BBC Science The Theory of (nearly) Everything 2019

(Martin Jones) #1
SYNTHETIC BIOLOGY

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  1. ANTI-MALARIAL WEAPONS
    More effective malaria drugs are on the horizon


Malaria has killed more humans than anything else in history. Up to
a million people still die from the disease each year and the WHO
estimates that the financial burden of treating malaria in sub-Saharan
Africa since the 1960s has been hundreds of billions of dollars.
Since the 17th century, we’ve tackled it with a series of treatments,
such as quinine and chloroquine with limited success. The problem
with this kind of serial medical monogamy is that the parasites
evolve resistance. For that reason, the most effective
treatment today is a cocktail of drugs, including the
key ingredient artemisinin. It’s an
extract from a sweet wormwood, an
Asian shrub that’s been used in folk
medicine for centuries. But wormwood
is finicky to grow and over the last few
years the artemisinin market has been
subject to boom and bust cycles, and
hence fluctuating supply and costs.

Enter Jay Keasling. While trying to design a genetic circuit that would
produce diesel in his labs at the University of California, Berkeley,
one of his students noticed that a by-product was closely related to
artemisinin and they decided to follow this up. Built from 12 genes
from three different organisms, the first successful cellular synthetic
artemisinin producer was published in 2006.
After major investment from The Bill and Melinda Gates Foundation
(as well as a number of other investors), the drug was
developed. Recently, market forces have hindered the
distribution to malaria zones, but this story marks
the first great product of synthetic biology.
The revolution has begun.

Lifeforms are much more complex than the most powerful
computers – but noisier too, meaning that the underlying
logic is not always linear, clean or obvious. Part of the work
of the synthetic biology movement has been to strip out
the noise of biological systems and reduce them to their
component parts, ready for re-building.
The result could be super-compact systems that can store
information for tens of thousands of years. Back in 2013,
there were a couple of high points in the computerisation of
biological circuits. In February, MIT scientists programmed a
circuit out of DNA that could store memory for up to 90 cell
generations – roughly nine days – using logic functions akin
to those in electronics. A month later, another team published
a system of DNA that works like a transistor – the essential
component behind all modern electronics.
In 2016, MIT scientists created a programming language,
allowing them to rapidly design complex, DNA-encoded
circuits that give new functions to living cells.


  1. CANCER ASSASSINS
    Genetic circuits to eradicate cancerous cells


The most effective ways to treat
cancers are still chemotherapy
and radiotherapy. Although these
techniques are getting more precise in
targeting malignant cells, they still kill
many healthy cells, making the patient
sick during their treatment.
Back in 2011, Ron Weiss and his
team at MIT designed a genetic circuit
that slots into a harmless virus,
which then infects a cell. Once in
there, it effectively asks the cell five
biological questions. If the answer
to any of these molecular queries is
negative, the circuit deactivates. If all
five answers are positive, the cell is

identified as cancerous and the
circuit activates the cell’s own
suicide programme. Compared
to the blunderbuss approach of
radiotherapy, this is a sniper. So far,
this only works in one type of cancer
cell, called HeLa, and only in a culture,
not yet in animal models.
More recently, researchers at the
University of California and MIT have
come up with another strategy. They
engineered a bacterium to produce
cancer drugs and then self-destruct,
releasing the drugs at a tumour. The
technique was tested on mice and
found to reduce tumour size.

A team at MIT has built DNA
circuits that can perform logic
operations and store the results


  1. BIO-COMPUTING
    Biological circuits could be the future


HeLa cancer cells in a
culture can be destroyed
by a genetic circuit

Red blood cells infected
with malaria parasites
in a blood sample taken
from a patient in Africa

by DR ADAM RUTHERFORD
(@AdamRutherford)
Dr Rutherford presents Radio 4’s Inside Science.
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