Humanity was forever set on an irreversible path when a curious Austrian started messing around with his garden plants. Mendel and his peas may have been a very basic and rudimentary grasp at understanding genetics but today, with all the modern tools and technology available to geneticists, they are able to experiment with accuracy and precision that is of several orders of higher magnitude than ever before. We are now able to actively change the DNA of organisms to achieve lots of interesting and downright baffling things. One of humanity’s greatest yet relatively unsung achievements is the development of CRISPR-Cas9. In fact, many of these achievements below wouldn’t be possible without it. If you want to learn more about this technology, check this some background reading. So here are some of the coolest things geneticists have achieved quite recently.
Quick biology question: How many nucleobases is DNA made of? The correct is answer is four – A, C, G, T. But now, scientists have successfully created bacteria that has DNA with 6 bases (the extra two being X and Y). “Why is that interesting?” you may ask, and it’s interesting, very interesting in fact, because it gives us a glimpse of how life actually formed out of the building boxes that were present in Earth’s soup of creation. It may even lead to humans being able to create synthetic life! Oh, the humanity!
Scripps Research Institute in California has had a team working on this exact same problem for a couple of years now. They had their first breakthrough in 2014, where they discovered the X and Y nucleobases. At that time, inserting them into an organism and hoping for it to survive was just a theoretical possibility but today, they have managed to achieve it. The team, headed by Dr. Floyd Romesberg, have been experimenting with a particular type of bacteria called E. Coli (it’s commonly found in your gut and is generally harmless; beneficial even, because it synthesises the vitamin B2, but some strains can cause you to have severe food poisoning).
They genetically modified the E. Coli to accept the X and Y bases as a part of their natural makeup and hold onto them for their whole lifetime. The real challenge was to keep the E. Coli from rejecting the new bases after some growth – all the early experiments ended up in failure because X and Y got rejected or the resulting organism was too weak and sickly to survive. Thanks to CRISPR, they reprogrammed the bacteria to not recognise the new bases as foreign bodies and this allowed the bacteria to better assimilate the bases. Right now, the bases don’t really do anything but that could change in the future – scientists can program different attributes into those bases and that could result in a totally different organism.
And that does sound slightly spooky. What if some mad scientist can now genuinely cackle in glee and cry out “It’s alive! It’s aliiiivvveeee?”, having created actual life inside a lab? But Dr. Romesberg assures that creating synthetic life isn’t feasible for a long time to come and even then, it won’t be anything as complex as an animal or human being. Our cell structure is just too complex to be easily modified. But what we should be looking at is the possibility of lab grown proteins. This definitely has the potential to revolutionise that field by creating a whole different variety of protein – perhaps we could even make lab grown bacon that tastes better than real bacon? Only time (and science!) will tell.
GIFs and photos in DNA
Scientists over at Harvard University have successfully encoded and decoded a GIF as well as a photo from the DNA of bacteria. That’s it, pack it up boys. The future is finally here.
Sounds right out of science fiction doesn’t it? The team over at Harvard managed this astounding feat from a rather innocuous bacterial response. The immune system of any organism, once it has finished fighting the threat of an incoming virus, adds a part of the virus to it’s own genetic code to better ‘remember’ how to fight it, should it encounter it again. Scientists created “fake” viruses that contain the pixels of the image encoded into its genetic makeup. In this particular trial, the team at Harvard used an image of the human hand as well as one of the most historic GIFs in the world – Sallie Gardner at a Gallop. They made these image coded viruses infect strains of E.Coli and let the genetic code copy them. (They broke the GIF down into 5 frames and fed a frame a day to the bacteria culture) Once this was done, they were able to reconstruct both the image and the GIF with over 90% accuracy from the bacteria’s genome!
This is truly amazing news. This could mean that bacteria could become our new storage medium in cases like measuring the impact of global warming in different places or having a living cell record what exactly is happening to it in real time – opening up all new avenues of study in different fields.
Clearing typos in embryos
CRISPR can be theoretically used to do a lot of amazing things, such as treating cancer, sickle cell anemia and even high cholesterol! Provided we figure out how to isolate the specific parts of the genetic code in our DNAs that end up causing these diseases. But recently, scientists have hit a huge milestone in developing CRISPR – being able to edit the ‘typo’ in the genetic code of a human embryo, thereby removing the chance of an inherited disease. One of Life Science’s most prestigious universities, Salk University in San Diego, California, in conjunction with the Oregon Health & Science University and Korea’s Institute for Basic Science, managed to successfully cut out the genetic code that would’ve lead to hypertrophic cardiomyopathy in an IVF embryo (colloquially known as a test tube baby) with no side effects. This has huge implications for our future, where babies can be monitored for any genetic diseases and ‘cured’ of them, even before birth. Perhaps, we can soon expect the scientists to figure out how to remove specific disease markers in the body, which make a person more predisposed to particular diseases. Either ways, this achievement needs to be lauded and appreciated just because of the millions of children in the future who needn’t go through a rough childhood due to an inherited disease.
CRISPR has a dark side
It’s not all roses. Researchers working on CRISPR trials on mice have cautioned the world that editing a particular stretch of a genetic code can have far-reaching and unthought-of side effects and mutations that may occur. One of these researchers, Stephen Tsang of Columbia University’s Medical Center says that, “We feel it’s critical that the scientific community consider the potential hazards of all off-target mutations caused by CRISPR, including single nucleotide mutations and mutations in non-coding regions of the genome,”. The researchers used CRISPR to successfully correct genetic blindness in mice but once they sequenced the whole genome after the trial, they found more than 1500 mutations and over 100 large gene sequence deletions and insertions that the computer’s predictive algorithm didn’t account for. While it is unclear right now what these mutations mean for the mice, chances are high that there could be some highly undesirable and downright dangerous side effects.
Does this mean that the CRISPR hype is dead? Thankfully, not. The researchers are still very optimistic about CRISPR. They just urge extreme caution when using the tool, especially since clinical trials on humans have started. The predictive algorithms still have a lot of optimisation and learning to do. “Researchers who aren’t using whole genome sequencing to find off-target effects may be missing potentially important mutations,” Dr. Tsang says. “Even a single nucleotide change can have a huge impact.” They hope that this study as well as their findings allow people to work on figuring out how to make CRISPR-Cas9 more specific and safer while editing genetic code. This is but a minor obstacle for a bright future.
Y’all got anymore of those designer babies?
Ah, designer babies. The removal of the pseudo RNG element out of childbirth and make it an RPG character creation simulation instead – “Ah yes, I would like my daughter to have +20 Speed and +42 Beauty please. And go easy on the Derp Factor”. A lot of new parents and parents-to-be would probably love to have this, and have this now and obviously, like literally everything else, the idea is also mired in controversy.
Childbirth in and of itself is a very polarising topic. When you add choosing characteristics into the mix, the polarisation goes up a notch. And there are valid arguments on both sides. The pro Designer Baby side argues that this could be the eventual, most beneficial evolution of mankind, making all babies supah smart, supah strong and supah beautiful. The collective IQ of the entire world goes up and the age old theory of the hot-crazy curve goes out the window.
Similarly, the Anti Designer Baby side say that it is going to create a horribly imbalanced world, where rich people’s children have a distinct physical advantage due to them being able to afford gene therapy, and thereby create one of the most visual and easy to see discriminations the world has ever seen after the Apartheid. Or on the flip side, if literally everyone got access to them in some years, it could reduce diversity and make everyone copies of everyone else. A standardised (dare we say communistic?) world, where everyone is equally beautiful, equally smart and no one has any of their special quirks or talents. We aren’t going to take any sides here, but what we ARE going to say is, this argument is pointless. At least for now. CRISPR-Cas9 (Yup, you’re going to be hearing about this a lot) while being quite effective, is still in it’s infancy. We are able to isolate and work on specific SINGLE genes at max, while each of the human traits such as intelligence depend on multitudes upon multitudes of genes that we don’t even know about. Even something very linear like height (whose cause and genes we are still learning about) could be caused by the combination of over 93,000 genetic mutations! For the record, we have identified only 700 of them. Even more damning to the cause is that CRISPR can’t introduce new genetic code to the code it ‘snips away’. The DNA automatically copies code from another part of the cell, so while this is extremely useful in cutting out diseased or troublesome parts, it makes introducing even a small mutation or new piece of code an extremely tall order. This is also a huge drawback to CRISPR because the single cell limitation means that we can only ‘cure’ diseases that occur due to a single specific gene mutation – thankfully there are enough of those, like for example Huntington’s Disease and sickle cell anemia. CRISPR isn’t going to advance to the level of combating the more complex diseases for a while yet, let alone mess around with human traits. Designer babies, for the better or worse, are still far off away.
Forget images, print viruses
Synthetic Genomics, a synthetic biology company based out of California has unveiled a machine that is capable of printing out viruses. No, not the computer kind. They call it the Digital to Biological Convertor (very imaginative name, we know). It uses a module that is already widely available called the BioXP 3200, which researchers use to digitally synthesise DNA. The Digital to Biological Convertor can use this digital DNA to assemble parts of the virus together and essentially ‘print’ it out. This has numerous uses – people can send samples of viruses digitally from places where there aren’t facilities available, we could send the machine to Mars for example and get it to print organisms there to test out hypotheses, the possibilities are endless. Digitally synthesised DNA can be a huge boost to remote medicine and if at a place equipped with the proper CRISPR-Cas9 tech, doctors from the other side of the globe will be able to ‘operate’ on you on the genetic code level in the future.
Space bear protein, good!
Scientists working over at the University of Tokyo have discovered that among all its varied remarkable abilities, Tardigrades (henceforth to be referred to as Space Bears… we mean, have you looked at them!?) have a special protein in their cells that protect them against X-Rays. But what’s cooler is that if you transfer this protein, human cells ALSO get the radiation shield. How cool is that?
This protein, called DSUP prevents the Tardigrade’s cell from disintegrating into mush when irradiated. Since such proteins are much easier to study when inserted into a mammalian cell, researchers tried a human cell culture and inserting DSUP into it. It ended up reducing about 40% of the damage against head on X-Ray irradiation. This opens up new ways to enhance radiation therapy for cancer patients by increasing the cell’s resistance level to the radiation. And the fact that this is just one protein of many in the Tardigrade genome, makes it all the more interesting. What more secrets does it hold?
This article was first published in the September 2017 issue of Digit magazine. To read Digit’s articles first, subscribe here or download the Digit app for Android and iOS. You could also buy Digit’s previous issues here.