Reconstructing the bacterial genomes from samples from the
Deepwater Horizon oil spill will allow us to understand which organisms
are involved in oil degradation. Image courtesy Benjamin Walther/University of Texas
Human genomics is just the beginning: the Earth has 50 billion tons of DNA. What happens when we have the entire biocode?
Dawn Field
is a fellow with the NERC Centre for Ecology and Hydrology, the
Biodiversity Institute in Oxford, and the Smithsonian Institution in
Washington, DC. Her latest book is Biocode: The New Age of Genomics.
In case you weren’t paying attention, a lot has been happening in the
science of genomics over the past few years. It is, for example, now
possible to read one human genome and correct all known errors. Perhaps
this sounds terrifying, but genomic science has a track-record in making
science fiction reality. ‘Everything that’s alive we want to rewrite,’
boasted Austen Heinz, the CEO of Cambrian Genomics, last year.
It was only in 2010 that Craig Venter’s team in Maryland led us into
the era of synthetic genomics when they created Synthia, the first
living organism to have a computer for a mother. A simple bacterium, she
has a genome just over half a million letters of DNA long, but the
potential for scaling up is vast; synthetic yeast and worm projects are
underway.
Two years after the ‘birth’ of Synthia, sequencing was so powerful
that it was used to extract the genome of a newly discovered,
80,000-year-old human species, the Denisovans, from a pinky bone found
in a frozen cave in Siberia. In 2015, the United Kingdom became the
first country to legalise the creation of ‘three-parent babies’ – that
is, babies with a biological mother, father and a second woman who
donates a healthy mitochondrial genome, the energy producer found in all
human cells.
Commensurate with their power to change biology as we know it, the
new technologies are driving renewed ethical debates. Uneasiness is
being expressed, not only among the general public, but also in
high-profile articles and interviews by scientists. When China announced
it was modifying human embryos this April, the term ‘CRISPR-CAS’
trended on the social media site Twitter. CRISPR-CAS, by the way, is a
protein-RNA combo that defends bacteria against marauding viruses.
Properly adapted, it allows scientists to edit strings of DNA inside
living cells with astonishing precision. It has, for example, been used
to show that HIV can be ‘snipped’ out of the human genome, and that
female mosquitoes can be turned male to stop the spread of malaria (only
females bite).
But one of CRISPR’s co-developers, Jennifer Doudna of the University
of California in Berkeley, has ‘strongly discouraged’ any attempts to
edit the human genome pending a review of the ethical issues. Well,
thanks to China, that ship has sailed. Indeed, now the technology
appears to be finding its way into the hands of hobbyists: Nature
recently reported that members of the ‘biohacker’ sub-culture have been
messing around with CRISPR, though the enthusiast they interviewed
didn’t appear to have a clear idea of what he wanted to do with it.
Given that our genetic abilities appear to be reaching a critical
threshold, it is worth taking a fairly hard-headed look at what the next
few years promise. For instance, could DNA solve some of our pressing
energy issues? One project hopes to engineer trees that glow in the
dark. You can sign up to preorder one now – at least the weed version of
it; trees take too long to mature to be good prototypes. Perhaps the
day is not far off when our streets are lined with bioluminescent
foliage. This would presumably drive electric streetlamps into
obsolescence, like so many other energy-hungry ‘old-fashioned’
technologies.
But this is hardly the only potentially revolutionary project that
aims to play out in the next five to 10 years. Venter is working on
re-engineering pig lungs so that they can be used in human transplants.
This could have a much larger impact than is immediately obvious: about
one in 10 deaths in Europe is caused by lung disease. Farther afield,
Venter is in the race to find life on Mars with DNA sequencers, and is
developing methods of ‘biological teleportation’ – the idea is that you
sequence microbial DNA on Mars and then reconstruct the genomes on Earth
using 3D printing. The process could work the other way around, too.
Venter and Elon Musk are talking of using this technology to terraform
Mars with 3D-printed earthly microbes. The whole thing boggles the
imagination, of course, but Venter and Musk do have form for pulling off
amazing feats. Nevertheless, perhaps we should start our tour of the
horizon closer to home.
By 2020, many hospitals will have genomic
medicine departments, designing medical therapies based on your personal
genetic constitution. Gene sequencers – machines that can take a blood
sample and reel off your entire genetic blueprint – will shrink below
the size of USB drives. Supermarkets will have shelves of home DNA
tests, perhaps nestled between the cosmetics and medicines, for
everything from whether your baby will be good at sports to the breed of
cat you just adopted, to whether your kitchen counter harbours enough
‘good bacteria’. We will all know someone who has had their genome
probed for medical reasons, perhaps even ourselves. Personal DNA stories
– including the quality of the bugs in your gut– will be the stuff of
cocktail party chitchat.
By 2025, projections suggest that we will have sequenced the genomes
of billions of individuals. This is largely down to the explosive growth
in the field of cancer genomics. Steve Jobs, the co-founder of Apple,
became one of the early adopters of genomic medicine when he had the
cancer that killed him sequenced. Many others will follow. And we will
become more and more willing to act on what our genes tell us. Just as
the actress Angelina Jolie chose to undergo a double mastectomy to stem
her chances of developing breast cancer, society will think nothing of
making decisions based on a wide range of genes and gene combinations.
Already a study has quantified the ‘Angelina Jolie effect’. Following
her public announcement, the number of women turning to DNA testing to
assess their risk for familial breast cancer doubled.
For better or worse, we will increasingly define ourselves by our
DNA. There are hints of this already in the issues of privacy
surrounding disease genes such as the ApoE gene, the largest known
genetic determinant of Alzheimer’s disease. In 2007, James Watson – one
of the discoverers of the structure of DNA – became the second person
ever to have his genome sequenced. He refused to learn whether he had
the ApoE gene, terrified that he would meet the same fate as his mother,
who died of dementia. At the other end of the spectrum, John Wilbanks, a
proponent of genomic openness, freely admitted that his profile carried
a risk of Alzheimer’s. Society will have to develop new norms to cope
with such dilemmas, but whether they will stick closer to the path of
Watson or Wilbanks remains to be seen.
Perhaps the most profound long-term societal change will be DNA’s
contribution towards what the American futurologist and entrepreneur
Peter Diamandis calls ‘perfect knowledge’. Diamandis seemed to be
thinking mainly about omnipresent cameras:
With a trillion sensors gathering data
everywhere (autonomous cars, satellite systems, drones, wearables,
cameras), you’ll be able to know anything you want, anytime, anywhere,
and query that data for answers and insights.
You can see what he means in certain areas already: for example,
geography. Due to satellite imaging, we can see the entire surface of
our planet. There can be no undiscovered land masses. The map of the
world is complete. And we should expect the same thing for genetics. DNA
testing will become so pervasive it will transform the medical, legal
and social foundations of society. If blanket genome sequencing takes
off, it will be impossible to obscure human relationships or ignore the
content of our DNA.
Unlawfully drop trash you’ve touch, licked or chewed, like gum or a tissue, and you might find a facsimile of your face on a bus stop
The tell-tale signs of the possible future are wide-spread. DNA
testing is already the gold standard of criminal evidence. It takes only
a hair, a fingerprint, or a glass that has been drunk from, to get
enough DNA to identify a suspect, and there are millions of DNA profiles
in the FBI’s CODIS database to match against. Some gated communities in
the United States require DNA from pets. Owners who let their pets
defile shared grounds are fined: the authorities only have to match what
they fail to scoop against their entry in the mandatory pet registry.
In Hong Kong the same goes for those who litter. Unlawfully drop trash
you’ve touch, licked or chewed, like gum or a tissue, and you might find
a facsimile of your face on a bus stop. The latest advances in DNA
identification permit life-like 3D reconstructions.
What next? Presumably a consolidated genomic registry isn’t far off.
It already exists to a limited extent, populated on a voluntary basis by
early adopters. There are several million-human genome projects. The
consumer genetics company 23andMe in California can boast more than
1 million customers. National genomics programmes are taking shape
across the globe, led by countries such as Iceland, which has now
sequenced or inferred the genomic content of a third of its population
on a voluntary basis – so far. Kuwait, on the other hand, recently
introduced mandatory DNA testing of its entire population as an
anti-terrorism measure.
The social and political consequences of such an archive frankly defy
my futurological abilities. A certain amount of alarm does not seem
misplaced, for if any technology lends itself to state or private abuse,
it is this one. But my interests are basically scientific, and while a
registry of the genome of every human on the planet would be one of the
most tremendous scientific assets ever created, it would still only
scratch the surface of what genomics might achieve.
We are beginning to think of the DNA on Earth as a whole.
All life, including humans, ultimately exists in one system, our Pale
Blue Dot. Let’s give it a name. Let’s call the sum of DNA on Earth ‘The
Biocode’.
Scientists have just estimated this Biocode’s size. Combining
information about genome size with information about the biomass of
different organisms suggests that the Biocode exceeds ±3.6 × 1031 million
base pairs. Multiplying the genome sizes of organisms, ranging from
bacteria to bees to birds, by the numbers of organisms in all groups of
life on Earth yields a (very rough) estimate of 50 billion tons of DNA.
This is enough of the invisible code of life to fill 1 billion shipping
containers.
How much do we know about it? Shockingly little. We remain
overwhelmed by its biodiversity, especially when it comes to the
invisible majority: microbes. Not only are we appreciating that our guts
are filled with trillions of microbial cells, but so is the planet.
Single-celled, microbial life comprises 50 per cent of the planet’s
biomass and 99 per cent of its genetic diversity. It is ancient, drives
our biogeochemical cycles, helps the planet sustain life, and is largely
unknown.
But that will change. One of the greatest achievements of the coming
century will be the characterisation of the Biocode, not just as a list
of genomes of different species, but as patterns of interacting
communities. Our first guess at its size opens a door. We will start to
understand how it has fluctuated in composition in the past and how it
will change in the future. We can start to learn how it works.
By 2050 we should aim to finally have a handle not only on human
genetic diversity but on the biodiversity of the planet. We will have
hopefully completed a DNA-based Systema Natura, the work that
Linnaeus, the father of taxonomy, first published in 1735. The key
question will be how much of the Earth’s genetic legacy will remain.
Projects such as the Smithsonian’s Global Genome Initiative are trying
to freeze samples from all extant organisms for future DNA sequencing,
both to await even cheaper costs and to protect genomes that might
become extinct prior to being read.
This updated edition of the Systema Natura should elucidate
not only the true evolutionary relationships between organisms, but also
the ways in which ecologically-related genomes interact. At the moment,
we are still largely at the inventory stage. We are reading the DNA of
everything from Neanderthals to woolly mammoths, to the microbes of the
New York subway system. Here’s one interesting area in which we have
been making progress, for example: we have a significant fraction of the
‘panda biocode’. This includes 2 per cent of the genomes of all extant
pandas, their primary food, bamboo, and samples of the panda microbiome,
a collection of microbes that can digest cellulose and thereby enable
this carnivore with canine teeth to live like a vegetarian on its
otherwise indigestible plant diet.
If all life has DNA and it is interlinked on our planet, then the entire planetary ecology can be likened to a giant computer
But we have a long way to go. There could be more than 20 million
species on Earth. The Earth Microbiome Project alone has catalogued some
9 million microbial species, and it is only one of an array of projects
sequencing the branches of the tree of life. This is Big Science
indeed; in fact, it is one of the biggest scientific enterprises in
history, the de facto Planetary Genome Project.
The authors who estimated the size of the Biocode seized on the
metaphor of DNA as software to produce a tremendous thought. If all life
has DNA and it is interlinked on our planet, then the entire planetary
ecology can be likened to a giant computer. For example, it is because
of life that Earth has an oxygen-filled atmosphere. Oxygen comes from
the DNA software in plants and microbes using sunlight and carbon
dioxide to drive the chemical process of photosynthesis. This
system-view of the planet allows us to make further daunting
calculations. Say that the processing power of this computer is the rate
at which information is processed from DNA sequence to proteins. This
suggests that our planet boasts computational power 1022
times that of China’s Tianhe‑2, which is currently the fastest
supercomputer ever built. Modern society is obsessed with computers, and
now we have to consider that we live inside one, at least in some
figurative sense. If we accept this analogy, we also have to accept that
we know little about how it works.
Of course, even as we are developing the
ability to decipher the code of this great computer, we are hacking away
parts of it, largely ignorant of the consequences. We face a sixth mass
extinction, defined as the loss of more than 75 per cent of the species
on Earth in a short geological time period. Ever since humans evolved,
we have been reprogramming the Biocode, but the pace is stepping up.
Never mind those notionally alarming genetics projects: we clear-cut
forests, plant mono-culture crops, hunt and fish prey to extinction,
poison vast tracts of remaining biodiversity or force its migration off
land we claim for ourselves. Now the pace of extinction alone might be
as high as 100 times background rates. In most cases, extinction is like
wiping clean a computer’s hard drive. The information is irretrievable.
Most who worry about the power of genomics fear the spectre of
designer babies, bio-terrorism, denial of insurance coverage,
discrimination based on DNA, or genetic surveillance. Perhaps we should
worry more about the fact that we are rewriting the code of life on
Earth at a terrifying pace, usually without even considering that this
is what we are doing.
By 2100, could the Biocode be significantly synthetic in nature? It
is not too far-fetched to suppose that we will see both the rise of
industrially produced bespoke creatures and the loss of naturally
occurring organisms born without the intervention of a computer. Whether
the future of genomics is set to be shadowed in darkness or bask in
bright light, what is perhaps the most incredible about its potential is
its reach. The Biocode has been crunching away on Earth since life
originated some 3.5 billion years ago. Pretty much regardless of what
humans do, it will surely continue well into the future in some form, no
doubt of mind-blowing complexity. It might even include new species of
human, wrought by the coming generation, whether by accident, design, or
some combination of the two.
11 September 2015
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