Despite being one of the most radical fields of human inquiry into the unknown, our current understanding of biotechnology has failed to keep up with the discipline’s tremendous potential. It’s understandable; the field and its overwhelming pace seemed to arrive out of nowhere. A scant 15 years ago the Human Genome Project was still decoding our 46 chromosomes; now, a subculture of “citizen biohackers” are editing their own genes. Lab Management & Science has put together a primer on the past, present and future of this pioneering field.
From beer to single-cell proteins
Turns out the use of biological processes to improve our lot is actually quite old. Probably the earliest example of biotechnology is the fermentation process, which gave us bread, cheese and beer. As is often the case, the military kickstarted innovation in the field when they needed to upscale fermentation processes to match the war effort. When Britain needed more acetone to produce more cordite for their artillery shells, they used a revolutionary method of turning maize into acetone via fermentation. Animal feed shortages could also be virtually eliminated by mass producing yeast, German scientists discovered during the war.
Large-scale factory farming was perhaps the most crucial biotechnology development of the early 20th century, since it enabled the massive population explosion we are still experiencing, mushrooming from 2 billion people in 1927 to 7.6 billion today. The application of biotechnology to the medical field resulted in penicillin and the mass production of steroids and cortisone by the 1950s, providing the impetus for the creation of new technologies that continue to increase human lifespan.
The latter half of the 20th century was inaugurated with a craze for single-cell proteins (SCPs), which it was hoped would end world hunger through an industrial-scale effort to grow edible microorganisms on oil. The Soviet Union even began to build factories to utilise this process next to their oil refineries. Public anxiety over traces of petroleum in these foods eventually caused the project to be scrapped.
There has always been a Utopian tinge to public perceptions of groundbreaking technologies, and this is especially true of biotechnology. But its failure to address the global food crisis via SCPs or solve the energy crises of the 1970s reduced faith in the biotech’s potential. It would take one of science’s true quantum leaps to inspire faith in the field again.
Crick and Watson, two affable chaps from King’s College London discovered the double helix structure of DNA in 1953, but it wasn’t until the early 70s that the practical application of gene technology came to be understood, thanks to the discovery that genes can not only be split into segments, but also spliced together in new ways, the latter technique being known as recombinant DNA.
The implications were enormous: not only is the inner structure of our microbiome an open secret, we can actually tinker with it to our heart’s content. This opened the door to tailor-made proteins, a vital early step in gene-based medicine, of which the Hepatitis B vaccine is a good example. Produced as a direct result of recombinant DNA, the vaccine is available for as little as R7.50 per dose in developing countries and has saved untold millions of lives.
As we’ve seen, biotechnology has mostly focused on innovations in food supply rather than therapeutics. It follows that a major outcome of the discovery of recombinant DNA was the creation of genetically modified organisms (GMOs). The implications of this technology hit supermarket shelves in the US in 1994, courtesy of the Flavr Savr tomato. Walk into a supermarket nowadays and over three-quarters of the fresh produce is genetically modified. As for those seed packets in the gardening section? Flip the packet over; many of them have a disclaimer at the back which reads ‘Contains genetically modified content. Not intended for human consumption.’
But alarmism helps no-one and GMOs have consistently increased global agricultural yields for years on end. Arguably, the risks outweigh the negatives, especially since future climate change models predict severe famines in developing countries. The possibility of modifying crops to be more resistant to changes in climate and possibly even grow at unusual times of year remains the best option to pre-empt this. New evidence even suggests that GMO crops can eliminate the need for pesticides, as demonstrated by Bt corn, a strain that even controls pests in non-GMO crops planted close by.
But the concern remains that GMOs could have unforeseen consequences, particularly since innovations in the field are driven almost entirely by market demands and not health policy. Scientists are now introducing kill switches into their GMOs that activate once they leave a designated area. While this was originally meant to stop harmful GMOs escaping a lab environment it is being used by huge agriculture consortiums such as Monsanto to prevent theft of their patented gene materials. Little thoughts is given to the potential weaponisation of such a technology, though.
Confused laymen have been scratching their heads for a while whenever the term CRISPR flashes across their screens. While the science underlying CRISPR can get rather byzantine, the technology itself is dead simple: identify and remove a sequence of the genome and replace it with one of your liking. The best, most expensive CRISPR kit on the market will currently set you back R2100 (plus shipping). Essentially, it’s a cheap, DIY recombinant DNA kit you could buy someone for Christmas.
The implications are so vast that they are perhaps impossible to grasp. Want to get rid of wrinkles? Theoretically, at least, nothing now prevents you from using CRISPR to increase the number of telomeres in your collagen cells. But our understanding of the genome has not kept pace with our ability to alter it, resulting in a situation in which unforeseen changes could wreak havoc. There is also no guarantee that genetic changes will remain confined to a single microbiome; the possibility of transferring catastrophically altered genes between organisms remains a very real threat.
Nonetheless, only 5% of the nearly 6000 diseases that are caused by genetic mutations can be treated by current conventional medicine. Sickle-cell anaemia can be attributed to a single error in the nearly three billion base pairs that comprise our DNA. The health benefits of CRISPR and new advances such as Cpf1 editing can’t be ignored and besides, Pandora’s Box, once opened, has never been closed before.
Induced pluripotent stem cells
A cell’s potency is its ability to change into other types of cell. It is particularly pronounced in stem cells that accompany the growing foetus in the womb. Cell potency is what scientists wished to harness in the early years of the 21st century when the reclamation of stem cells from aborted foetuses was floated, but that initiative was dead in the water as soon as religious conservatives in the US’ Bush administration caught wind of it.
But a Nobel-winning discovery by Shinya Yamanaka and Sir John Gurdon has demonstrated how adult stem cells can be changed into pluripotent stem cells that can replicate themselves and replace or supplement other cells. This raises the possibility of rapid tissue regeneration beyond anything dreamed of a mere decade ago.
One potential application of pluripotent stem cells is the growth of custom-made replacement organs (or entire limbs) in a laboratory. One problem with this technology that has so far prevented its widespread commercialisation is its tendency to cause teratoma (tumors) in laboratory mice.
The increased availability of technologies such as CRISPR have made it possible for anyone to take part in the biotech revolution, but the genome is a complex subject and acquiring enough knowledge to make informed choices about which parts of the genome to change requires a significant time investment. This is why the formulation of a genetics and gene coding syllabus is being floated as a necessity.
School science syllabi have traditionally been a decade or so behind current scientific practice, but given the current rate of scientific progress and the rise of “citizen biohackers” armed with CRISPR kits and too much time on their hands, the time to educate the public about these technologies was yesterday. The effort has begun, however, with books like Dr Natalie Kuldell’s BioBuilder teaching students to craft their own glowing bacteria and other experiments.
The possibility is very real that the current wave of biotechnologies are merely the initial stages of the next great technological revolution, similar to the computer revolution of the last half of the previous century. Whether we have passed the floppy disk stage yet remains to be seen, but one thing is certain: the future will be beyond belief.