The patient known as P2 is just 18 years old, but he has been receiving monthly blood transfusions since the age of 3. P2 has a genetic disorder called beta-thalassaemia. Thanks to a double whammy of faulty genes, he can’t produce working versions of haemoglobin, the protein that allows red blood cells to carry oxygen around the body. Regular transfusions were the only things that kept him alive but for the last 21 months, he hasn’t needed them.
An international team of scientists have managed to partially correct his genetic faults, granting him his independence. It’s a major victory for gene therapy, the act of editing faulty genes within living cells in order to treat diseases.
Walk among the Arctic ice and you’ll sometimes encounter distinctive patches of red snow. They’re caused by a species of bacteria called Colwellia psycherythraea. It’s a cold specialist – a cryophile – that can swim and grow in extreme subzero temperatures where most other bacteria would struggle to survive. Colwellia’s cold-tolerating genes allow it to thrive in the Arctic, but Barry Duplantis from the University of Victoria wants to use them in human medicine, as the basis of the next generation of anti-bacterial vaccines.
Colwellia’s fondness for cold comes at a price – it dies at temperatures that most other bacteria cope with easily. By shoving Colwellia genes into bacteria that cause human diseases, Duplantis managed to transfer this temperature sensitivity, creating strains that died at human body temperature. When he injected these heat-sensitive bacteria into mice, they perished, but not before alerting the immune system and triggering a defensive response that protected the mice against later assaults. The Colwellia genes transformed another species of bacteria from a cause of disease into a vaccine against it.
In a Japanese laboratory, a group of scientists is encouraging a rapidly expanding amoeba-like blob to consume Tokyo. Thankfully, the blob in question is a “slime mould” just around 20cm wide, and “Tokyo” is represented by a series of oat flakes dotted about a large plastic dish. It’s all part of a study on better network design through biological principles. Despite growing of its own accord with no plan in mind, the mould has rapidly produced a web of slimy tubes that look a lot like Tokyo’s actual railway network.
The point of this simulation isn’t to reconstruct the monster attacks of popular culture, but to find ways of improving transport networks, by recruiting nature as a town planner. Human societies depend on good transport networks for ferrying people, resources and information from place to place, but setting up such networks isn’t easy. They have to be efficient, cost-effective and resistant to interruptions or failure. The last criterion is particularly challenging as the British public transport system attests to, every time a leaf or snowflake lands on a road or railway.
Living thing also rely on transport networks, from the protein tracks that run through all of our cells to the gangways patrolled by ant colonies. Like man-made networks, these biological ones face the same balancing act of efficiency and resilience, but unlike man-made networks, they have been optimised through millions of years of evolution. Their strategies have to work – if our networks crash, the penalties are power outages or traffic jams; if theirs crash, the penalty is death.
To draw inspiration from these biological networks, Atsushi Tero from Hokkaido University worked with the slime mould Physarum polycephalum. This amoeba-like creature forages for food by sending out branches (plasmodia) from a central location. Even though it forms vast, sprawling networks, it still remains as a single cell. It’s incredibly dynamic. Its various veins change thickness and shape, new ones form while old ones vanish, and the entire network can crawl a few centimetres every hour.
For a mindless organism, the slime mould’s skill at creating efficient networks is extraordinary. It can find the most effective way of linking together scattered sources of food, and it can even find the shortest path through a maze. But can it do the same for Tokyo’s sprawling cityscape?
Tero grew Physarum in a wet dish at a place corresponding to Tokyo, with oat flakes marking the locations of other major cities in the Greater Tokyo Area. Physarum avoids bright light, so Tero used light to simulate mountains, lakes and other prohibitive terrain on his miniature map. The mould soon filled the space with a densely packed web of plasmodia. Eventually, it thinned out its networks to focus on branches that connected the food sources. Even by eye, these final networks bore a striking similarity to the real Tokyo rail system.
The mould’s abilities are a wonder of self-optimisation. It has no sense of forward-planning, no overhead maps or intelligence to guide its moves. It creates an efficient network by laying down plasmodia indiscriminately, strengthening whatever works and cutting back on whatever doesn’t. The approach seems as haphazard as a human planner putting railway tracks everywhere, and then removing the ones that aren’t performing well. Nonetheless, the slime mould’s methods (or lack thereof) produced a network with comparable cost, efficiency and tolerance for faults to the planned human attempt.
Tero tried to emulate this slime mould’s abilities using a deceptively simple computer model, consisting of an randomly meshed lattice of tubes. Each tube has virtual protoplasm flowing through it, just as the branches of the slime mould do. The faster the flow rate, the wider the tube becomes. If the flow slows, the tubes thin and eventually disappear.
Tweaking the specific conditions of the model produced networks that were very similar to those of both live Physarum and Tokyo’s actual rail system. Tweaking it further allowed Tero to boost the system’s efficiency or resilience, while keeping its costs as low as possible. This, perhaps, is the engineering of the future – a virtual system inspired by a biological one that looks a lot like a man-made one.
Reference: Tero et al. 2010. Rules for Biologically Inspired Adaptive Network Design. Science 10.1126/science.1177894
More on slime moulds: Predatory slime mould freezes prey in large groups
Images: from AAAS/Science
For centuries, farmers have been genetically modifying their plants without even knowing it. That’s the message from German scientists who found that grafting, a common technique used to fuse parts of two plants together, causes the two halves to swap genes with each other.
Grafting can involve fusing the stem of one plant (the scion) to the roots of another (the stock), or a dormant bud to another stem. There are many reasons for this – sometimes it’s the most cost-effective way of cultivating the scion, sometimes the stock has properties that the scion lacks including hardiness or sturdiness. The vessels of the two halves eventually merge but people have long believed that they keep their genetic material to themselves. It turns out they were wrong.
Sandra Stegemann and Ralph Bock from the Max-Planck Institute tested the theory by grafting two strains of genetically engineered tobacco plant. A Samsun NN strain had its main genome loaded with a gene that produced a glowing yellow protein, and another that made the plant resistant to the antibiotic kanamycin. The second Petit Havana strain was engineered to produce a glowing green protein, and be resistant to spectinomycin, another antibiotic. These genes were shoved into the genome of its chloroplast, the small structures that allow plant cells to photosynthesise and that contain their own separate genetic material.
Once the plants had merged, Stegemann and Bock found that the point of fusion was rife with cells that produced both glowing proteins and shrugged off both antibiotics. They cut slices from the plant and grew them in liquid that contained both kanamycin and spectinomycin for a month. While chunks that were taken from other parts of the plant fared poorly under these conditions, many of those from the graft site thrived, even producing fresh shoots.
With current technology, could we clone a mammoth? Cloning techniques have made significant progress in recent years and at least one well-preserved specimen has been found. But the same freezing process that preserves the bodies of many extinct mammals would also be the undoing of cloning endeavours. Ice destroys cells, puncturing their membranes, bursting them and exposing their contents. Upon thawing, the dead cells would be useless as a basis for cloning.
Until now, the destructive power of ice seemed like an insurmountable obstacle, dashing the prospect of “resurrecting” frozen extinct animals or preserving endangered ones. But a Japanese team have made a technical breakthrough that could both into more realistic visions. They have managed to breed healthy cloned mice from thawed bodies that have been frozen for 16 years. It’s quite literally a small start, but an important one.
A typical procedure for cloning is as follows. Take a living cell from a donor animal and fuse it with an ‘empty’ egg cell that lacks a nucleus – the central part of the cell that contains the DNA. The result is an egg that contains the donor’s genetic information, which can then be implanted into a surrogate mother. For this recipe, thawed cells from frozen tissues make poor ingredients; with their shredded membranes, they cannot fuse with other cells.
Sayaka Wakayama and colleagues from RIKEN in Japan solved the problem by developing a way of directly injecting the nucleus of a donor cell into the empty egg, broken membranes be damned. At first, they tested their method using cells taken from mice that had been frozen at -20C for a week. Even though the thawed bodies were bereft of living cells, the technique worked and while the success rate was low, there were successes nonetheless.
Fighting malaria with mosquitoes seems like an bizarrely ironic strategy but it’s exactly what many scientists are trying to do. Malaria kills one to three million people every year, most of whom are children. Many strategies for controlling it naturally focus on ways of killing the mosquitoes that spread it, stopping them from biting humans, or getting rid of their breeding grounds.
But the mosquitoes themselves are not the real problem. They are merely carriers for the true cause of malaria – a parasite called Plasmodium. It suits neither mosquitoes nor humans to be infected with Plasmodium, and by helping them resist it, we may inadvertently help ourselves. With the power of modern genetics and molecular biology, scientists have produced strains of genetically engineered mosquitoes that cannot transmit the malarial parasite.
These ‘GM-mosquitoes’ carry a modified gene – a transgene – that produces chemicals which interfere with Plasmodium‘s development. Rather than being suitable carriers, the bodies of the modified mosquitoes spell death for any invading Plasmodium.
But scientists can’t very well change the genes of every mosquito in the tropics. To actually reduce the burden of malaria, the genetic changes that induce malaria resistance need to be spread throughout the mosquito population. The easiest way to do this is, of course, to let the insects do it themselves. And Mauro Marrelli and colleagues from the Johns Hopkins University have found that they are more than up to the task.
The world is currently home to 6.5 billion people and over the next 50 years, this number is set to grow by 50%. With this massive planetary overcrowding, Band Aid’s plea to feed the world seems increasingly unlikely. Current food crops seem unequal to the task, but scientists at Texas University may have developed a solution, a secret ace up our sleeves – cotton.
Cotton is famed for its use in clothes-making and has been grown for this purpose for over seven millennia. We do not think of it as a potential source of food, and for good reason. The seeds of the cotton plant are rife with a potent poison called gossypol that attacks both the heart and liver. Only the multi-chambered stomachs of cattle and other hooved animals can cope with this poison, relegating cottonseed to a role as animal feed.
Getting rid of gossypol could contribute towards reducing the world’s hunger crisis. A fifth of a cottonseed’s weight is made up of oil, and a quarter of high-quality protein, and for every kilogram of fibre, each cotton plant produces 1.65 kg of seed. The plant is a worldwide crop, grown in over 80 countries by some 20 million farmers, the majority of whom live in the poorest parts of the world where starvation is an ever-looming threat. If only the seeds could be made edible.
Genetically modified crops have received a frosty welcome in the UK, and more widely in Europe. Those opposed to such crops worry (among other things) that they could affect the flora around them by outcompeting them or by spreading their altered genes in a round of genetic pass-the-parcel. Now, a new study shows that genetically-modified crops does affect surrounding plants – but in a positive way.
Kong-Ming Wu from the Chinese Academy of Agricultural Sciences found that genetically modified cotton designed to kill an insect pest can also protect other species plants from its jaws. In doing so, this “Bt cotton” could help to reduce the need and demand for other sprayed insecticides.
Bt cotton has been loaded with insect-killing genes taken from a bacterium called Bacillus thuringiensis (hence “Bt”). This species lives in soil and the surface of plants, and it produces crystals of proteins that are toxic to hungry insects. If they are swallowed, they stick to molecules in the pest’s gut, breaking down its lining and allowing both B.thuringiensis spores and colonies of normal gut bacteria to invade. It’s this wanton spread of bacteria that kills the animal.
Imagine reading the paper to find that a new wonder drug has been created that could save your life, if only you could afford it. Alternatively, put yourself in the shoes of the authorities that must decide not to offer powerful new drugs on the NHS because they simply aren’t cost-effective enough. These situations are all too common-place and are often due to the extremely high costs of drug development. But a couple of years ago, scientists at Icon Genetics and Bayer Bioscience made an exciting step toward lowering these costs for some of the most promising new treatments.
The treatments in question are called ‘monoclonal antibodies’ or ‘MAbs’, synthetic versions of the natural antibodies that our immune systems use to identify and neutralise infectious agents. MAbs are specially shaped to act like molecular gloves, sticking onto a target of choice and inactivating it by blocking interactions with other molecules.
The most famous member of this group, the breast cancer drug Herceptin, is one of a handful of currently available MAbs. But they are about to be joined by many more – over 150 MAbs are in development and the market for them is likely to exceed £10 billion.
But no matter how good these new biotechnological wunderkinds are, they will be worthless unless they reach the patients they are designed to benefit. And with the cost of treatment courses exceeding tens of thousands of pounds, that is looking unlikely. Every stage of the manufacturing process from raw materials to equipment is exorbitantly expensive and drives the inflated prices of the end product. As such, only better, cheaper and more effective production methods will enable scientists to fully realise the potential of these designer molecules. A new technique called ‘magnifection’ could be just such a method.