A Redesigned Planet?

Given the speed of change in the development of new technologies mentioned in this book such as genome editing, optogenetics, stem cell organoids, and synthetic biology, it is hard to predict exactly how radically these technologies are likely to transform our lives in coming decades. What is clear is that as exciting as the new biotechnologies are in terms of their impact on medical research, medicine, and agriculture, they also raise a whole number of socio-political and ethical issues. These include concerns about whether monkeys engineered to have genetic similarities to humans might lead to a ‘Planet of the Apes’ scenario, and fears about ‘designer babies’ being produced in the future to have greater beauty, intelligence or sporting skill. Although one potentially positive new development is the rise of a ‘biohacker’ movement which seeks to make molecular biology more accessible to ordinary people, there are also fears that in the wrong hands genome editing might be used to create new types of biological weapons for terrorist organisations. While such fears should not be dismissed as just an overreaction, to some extent they rest on an underestimation of the complexity of the Iink between the human genome and looks, intelligence, and sporting ability, or of the difficulties involved in creating a deadly virus that is worse than naturally occurring ones. Ultimately, the best way to ensure that new technologies are used for human benefit, not harm, is to take part in an informed debate and use public lobbying to argue for them to be developed safely, ethically, and responsibly.

Regenerating Life

Stem cells, which are ‘immortal’ cells that divide indefinitely and produce many different cell types, are central to how our body develops and maintains itself. Embryonic stem cells can give rise to all cell types in the body, and there has been lots of interest since their discovery in the 1980s in using such cells to generate new tissues or organs to replace diseased or faulty ones. More recently has come the discovery of induced pluripotent stem cells, which are normal skin cells taken from a person and genetically modified or tweaked chemically to give them stem cell properties. There is now hope that both of these types of stem cells might be used in ‘regenerative’ medicine, for instance in producing pancreatic cells that secrete insulin which could be used to treat diabetes. Perhaps the most remarkable breakthrough in recent years has been the discovery that stem cells introduced into a 3D matrix that is infused with chemicals that stimulate the development of particular cell types, can spontaneously form ‘organoids’, which have many of the cell types and even structural features of human organs such as hearts, kidneys, intestines, and even eyes and brains. Organoids make it possible to study how human organs develop but also this area of science raises many ethical issues. For instance, currently human brain organoids can only grow to the size of an embryonic brain, but if in the future they could be induced to grow to adult brain size, could they develop feelings and thoughts?

Light as a Life Tool

Visual light, and radiation of other frequencies, are highly important for scientific research. The first light microscopes made it possible for the first time to see that organisms from plants to humans are composed of cells. Electron microscopes have allowed scientists to study the structural components of cells in great detail, and even determine the shapes of individual proteins. Many lifeforms also use light to attract a mate or prey, or deter an attacker. Following the identification of the gene coding for the fluorescent protein that makes certain jellyfish glow green it has become possible to use this to genetically label proteins in a living cell, or even a live animal. This means that now the location of proteins in a cell can be determined exactly. A major recent step forward in neuroscience came with the discovery of protein channels in algae that conduct ions in response to light. By creating transgenic mice that have these proteins in their brain neurons, it is now possible to modulate the activity of these neurons by shining light into the brain though microscopic fibre optic cables. This new science of optogenetics allows neurons to be switched on or off experimentally. The optogenetic approach has been used to uncover the neural circuits involved in memory, pain and pleasure. In the future this technique might be used to treat physical pain or depression in people. Controversially, it might be also be misused, to supress memories, or even create completely false ones in people’s heads.

The Molecular Farm

Despite many inequalities in the world, it is a testament to human technology that modern agriculture is able to feed the 8 billion people on the planet. However, recently extreme weather patterns linked to global warming have been having an adverse effect on crops and farmed animal production, leading to fears about whether agriculture can continue to feed all the humans on the planet. Genome editing looks set to revolutionise agriculture by making it possible to precisely edit the genomes of farm plants and animals rapidly and economically in an unprecedented way. Such editing could be used to create vegetables and meat with enhanced flavour or nutrition. It could also be used to create disease resistant plants and animals, and reduce the use of antibiotics or pesticides. Looking further into the future it might eventually be possible to use genome editing to reconfigure plants or animals to survive in increasingly extreme types of climates. Despite these positive ways of using genome editing in agriculture, concerns have been raised about the safety of food produced from genome edited animals and plants, and potential adverse effects on animal welfare. Another criticism is that genome editing may only benefit giant agribusiness companies, and not ordinary farmers and consumers. Yet against this criticism, one of the revolutionary aspects of genome editing is how easy and economical it is to use, which means that unlike previous GM technologies, there is no reason why it cannot be used in a local, sustainable, and accessible way.

Next Year’s Models

Animal ‘models’ of health and disease have been central to biomedical science since at least when William Harvey used dogs to illustrate the fact that blood is pumped by the heart through the arteries and then through the veins back to the heart. In the 1980s, a major step forward came with the discovery of embryonic stem cells and ways to manipulate these genetically and then inject into mouse embryos, resulting in the creation of knockout and knockin mice with deletions, or more subtle changes, in specific genes. Unfortunately, it has been impossible to isolate embryonic stem cells from any other species besides mice, and more recently rats and humans. Yet rodents are far from the best animals for modelling, say the body’s metabolism or heart function and disease, or brain function and mental disorders. Instead, pigs and primates are potentially far better models for these respective areas of research. CRISPR/Cas genome editing has made it possible for the first time to create precisely genome edited versions of pigs, monkeys, and any other species that may provide a better model of specific aspects of human health and disease, than rodents. So genetically modified pigs might be used to study heart disease, but also provide hearts for human transplantation, while GM monkeys might help us better understand the biological basis of mental disorders such as depression or schizophrenia. However, this area of research is raising ethical issues about the creation of monkeys with human versions of particular genes, and how this might affect their behaviour and personality.

Life as a Machine

Bacteria are a source of many of the tools used in biotechnology. A technique called the polymerase chain reaction, or PCR, made it possible for the first time to amplify tiny starting amounts of DNA and has revolutionised medical diagnosis, testing of IVF embryos for mutations, and forensic science. PCR involves the repeated generation of DNA from a starting sequence in a cycle, one stage of which occurs at boiling point. Because of this PCR uses a DNA polymerase enzyme purified from an ‘extremophile’ bacterium that lives in hot springs. More recently scientists have constructed artificial bacterial or yeast genomes from scratch. The next step will be to create reconfigured bacteria and yeast with enhanced characteristics for use in agriculture, energy production, or generation of new materials. Some scientists are now seeking to expand the genetic code itself. The DNA code that human beings share with all other species on the planet has four ‘letters’, A, C, G, and T, which pair as A:T and C:G to join the two strands of the DNA double helix. And each particular triplet of DNA letters, for instance CGA, or TGC, codes for a specific amino acid, the 20 different amino acids joining together in a specific sequence to make up a particular protein. Scientists have now developed a new DNA letter pair, X:Y. By introducing this into an artificial bacterial genome, it is becoming possible to create many more amino acids than the current 20 naturally occurring ones, and thereby allowing many new types of proteins.

New Gene Therapy

Modern medicine has advanced tremendously in the 20th century, yet many people still die each year from conditions like heart attacks, cancer, and infectious diseases. Genome editing looks set to transform clinical medicine over the next few decades, because it now makes it possible to alter genes either in a living person, or in an infectious agent like a virus. One particular type of disease where genome editing is likely to have a big impact is single gene disorders such as cystic fibrosis, Huntington’s disorder, and muscular dystrophy. Because these disorders are due to a mutation in a single gene, there is hope that it should be possible to use genome editing to ‘correct’ the mutation in the cells of a sufferer. But genome editing also offers much promise for the treatment of more common disorders such as cancer. In the latter case, a mutated oncogene could be corrected by genome editing, or this approach used to enhance the ability of special immune cells in the body that target cancer cells. Genome editing also has much potential for targeting viruses like as HIV. In this case, there are two possible approaches. One involves targeting the HIV genome sequence, the other involves creating a mutation in a gene coding for a human protein that HIV uses to get inside an infected person’s cells. Bacterial infections might also one day be targeted by genome editing. However, many practical obstacles remain, the main one being how to get genome editing tools into a person safely.

The Gene Scissors

We are currently in the middle of a revolution in the biological sciences. The genome project made it possible to read the sequence of individual genomes, but what was lacking until recently was a way to rewrite particular genes in a living cell in an accurate, rapid, and economical fashion. This is now possible thanks to the invention of molecular ‘scissors’, based on natural mechanisms in the cell, that make it possible to cut the genome at a particular point, after which the cell’s own natural repair mechanisms edit the gene as directed. The most revolutionary of the molecular scissors is one called CRISPR/Cas. This is based on a process discovered in bacteria that normally acts to destroy viruses that invade the bacterium. Reprogrammed, CRISPR/Cas now makes it possible to accurately edit the genome of any living cell of practically any species, for a fraction of the time and cost required by other genome editing approaches. Not only can this approach be used to edit the sequence of genomes but also to switch genes on or off at will. CRISPR/Cas is revolutionising medical research and looks set to do the same for clinical medicine and agriculture. But it is also the source of much controversy as recently a scientific team in China used this approach to create genome edited babies, and in general some people fear the speed at which this new technology is developing and its potential for misuse. These are all issues that are explored in subsequent chapters of this book.

Supersize My Mouse

Although human beings have been altering genomes by selection and breeding of particular animal or plant variants for thousands of years, and X-rays and chemicals were first used to create mutants in the early 20th century genetic engineering in the true sense only became possible much more recently. First, the discovery that genes are made of DNA, revealed the material nature of the genome. Second, scientists in the early 1970s discovered enzymes in bacteria that can be used to cut and paste DNA in the test tube. Using such molecular ‘tools‘ bacteria were engineered to produce important medical products such as human insulin for diabetics, and from this was born what would become a billion-dollar biotechnology industry. A further important development was the discovery of embryonic stem cells and manipulation of these to make ‘knockout’ mice that had a deletion of a specific gene, or ‘knockin’ mice that had subtle changes in a gene. However such an approach was still relatively expensive and time-consuming, and cold only be applied to mice. And although gene constructs could be introduced into cells in a less precise manner, the crude nature of this approach limited its application for both agriculture and gene therapy. In both areas of application there have been concerns about the safety and ethics of using such an approach. A major criticism has been the lack of precision in where a gene construct would end up the genome, leading to concerns about possible adverse effects.

Natural Born Mutants

Although direct engineering of animal and plant genomes only became possible from the 1970s onwards, people have been indirectly changing other species’ genetic make-up for thousands of years. This is because with the agricultural revolution that began 12,000 years ago, human beings began selecting particular variants of a species, and cultivating them as crops or breeding them as farm animals, and in the process altered a species’ genome over time. In fact this process began even earlier, with the domestication of the wolf, which eventually became our most faithful companion, the dog. And now modern genome analysis techniques are making it possible to understand how at the genetic level a dog or cat differs from their wild ancestors, or how wild boars became pigs, or wild grass could over time give rise to wheat, barley, or rice. In medical research, scientists realised that understanding how genes work could be helped by studying naturally occurring mutants. By studying how mutations affected an organism such as a fruit fly,genes involved in particular functions could be identified. A breakthrough was made when it was realised that treatment of fruit flies with X-rays dramatically increased the numbers of mutants. Today, X-rays and chemical treatments can be used to create mutant mice, and studies of such mice has identified genetic links with conditions such as congenital deafness.