The Brave New World of Using DNA to Store Data
A panoramic view of DNA
Netscape co-founder-turned-venture capitalist billionaire investor Marc Andreessen once posited that software was eating the world. He was right, and the takeover of software resulted in many things. One of them is data. Lots and lots and lots of data. In the previous two years, humanity created more data than it did during its entire existence combined, and the amount will only increase. Think about it: The hundreds of 50KB emails you write a day, the dozens of 10MB photos, the minute-long, 350MB 4K video you shoot on your iPhone X add up to vast quantities of information. All that information needs to be stored. And that's becoming an issue as data volume outpaces storage space.
The race is on to find another medium capable of storing massive amounts of information in as small a space as possible.
"There won't be enough silicon to store all the data we need. It's unlikely that we can make flash memory smaller. We have reached the physical limits," Victor Zhirnov, chief scientist at the Semiconductor Research Corporation, says. "We are facing a crisis that's comparable to the oil crisis in the 1970s. By 2050, we're going to need to store 10 to the 30 bits, compared to 10 to the 23 bits in 2016." That amount of storage space is equivalent to each of the world's seven billion people owning almost six trillion -- that's 10 to the 12th power -- iPhone Xs with 256GB storage space.
The race is on to find another medium capable of storing massive amounts of information in as small a space as possible. Zhirnov and other scientists are looking at the human body, looking to DNA. "Nature has nailed it," Luis Ceze, a professor in the Department of Computer Science and Engineering at the University of Washington, says. "DNA is a molecular storage medium that is remarkable. It's incredibly dense, many, many thousands of times denser than the densest technology that we have today. And DNA is remarkably general. Any information you can map in bits you can store in DNA." It's so dense -- able to store a theoretical maximum of 215 petabytes (215 million gigabytes) in a single gram -- that all the data ever produced could be stored in the back of a tractor trailer truck.
Writing DNA can be an energy-efficient process, too. Consider how the human body is constantly writing and rewriting DNA, and does so on a couple thousand calories a day. And all it needs for storage is a cool, dark place, a significant energy savings when compared to server farms that require huge amounts of energy to run and even more energy to cool.
Picture it: tiny specks of inert DNA made from silicon or another material, stored in cool, dark, dry areas, preserved for all time.
Researchers first succeeded in encoding data onto DNA in 2012, when Harvard University geneticists George Church and Sri Kosuri wrote a 52,000-word book on A, C, G, and T base pairs. Their method only produced 1.28 petabytes per gram of DNA, however, a volume exceeded the next year when a group encoded all 154 Shakespeare sonnets and a 26-second clip of Martin Luther King's "I Have A Dream" speech. In 2017, Columbia University researchers Yaniv Erlich and Dina Zielinski made the process 60 percent more efficient.
The limiting factor today is cost. Erlich said the work his team did cost $7,000 to encode and decode two megabytes of data. To become useful in a widespread way, the price per megabyte needs to plummet. Even advocates concede this point. "Of course it is expensive," Zhirnov says. "But look how much magnetic storage cost in the 1980s. What you store today in your iPhone for virtually nothing would cost many millions of dollars in 1982." There's reason to think the price will continue to fall. Genome readers are improving, getting cheaper, faster, and smaller, and genome sequencing becomes cheaper every year, too. Picture it: tiny specks of inert DNA made from silicon or another material, stored in cool, dark, dry areas, preserved for all time.
"It just takes a few minutes to double a sample. A few more minutes, you double it again. Very quickly, you have thousands or millions of new copies."
Plus, DNA has another advantage over more traditional forms of storage: It's very easy to reproduce. "If you want a second copy of a hard disk drive, you need components for a disk drive, hook both drives up to a computer, and copy. That's a pain," Nick Goldman, a researcher at the European Bioinformatics Institute, says. "DNA, once you have that first sample, it's a process that is absolutely routine in thousands of laboratories around the world to multiply that using polymerase chain reaction [which uses temperature changes or other processes]. It just takes a few minutes to double a sample. A few more minutes, you double it again. Very quickly, you have thousands or millions of new copies."
This ability to duplicate quickly and easily is a positive trait. But, of course, there's also the potential for danger. Does encoding on DNA, the very basis for life, present ethical issues? Could it get out of control and fundamentally alter life as we know it?
The chance is there, but it's remote. The first reason is that storage could be done with only two base pairs, which would serve as replacements for the 0 and 1 digits that make up all digital data. While doing so would decrease the possible density of the storage, it would virtually eliminate the risk that the sequences would be compatible with life.
But even if scientists and researchers choose to use four base pairs, other safeguards are in place that will prevent trouble. According to Ceze, the computer science professor, the snippets of DNA that they write are very short, around 150 nucleotides. This includes the title, the information that's being encoded, and tags to help organize where the snippet should fall in the larger sequence. Furthermore, they generally avoid repeated letters, which dramatically reduces the chance that a protein could be synthesized from the snippet.
"In the future, we'll know enough about someone from a sample of their DNA that we could make a specific poison. That's the danger, not those of us who want to encode DNA for storage."
Inevitably, some DNA will get spilt. "But it's so unlikely that anything that gets created for storage would have a biological interpretation that could interfere with the mechanisms going on in a living organism that it doesn't worry me in the slightest," Goldman says. "We're not of concern for the people who are worried about the ethical issues of synthetic DNA. They are much more concerned about people deliberately engineering anthrax. In the future, we'll know enough about someone from a sample of their DNA that we could make a specific poison. That's the danger, not those of us who want to encode DNA for storage."
In the end, the reality of and risks surrounding encoding on DNA are the same as any scientific advancement: It's another system that is vulnerable to people with bad intentions but not one that is inherently unethical.
"Every human action has some ethical implications," Zhirnov says. "I can use a hammer to build a house or I can use it to harm another person. I don't see why DNA is in any way more or less ethical."
If that house can store all the knowledge in human history, it's worth learning how to build it.
Editor's Note: In response to readers' comments that silicon is one of the earth's most abundant materials, we reached back out to our source, Dr. Victor Zhirnov. He stands by his statement about a coming shortage of silicon, citing this research. The silicon oxide found in beach sand is unsuitable for semiconductors, he says, because the cost of purifying it would be prohibitive. For use in circuit-making, silicon must be refined to a purity of 99.9999999 percent. So the process begins by mining for pure quartz, which can only be found in relatively few places around the world.
Gene Transfer Leads to Longer Life and Healthspan
In August, a study provided the first proof-of-principle that genetic material transferred from one species to another can increase both longevity and healthspan in the recipient animal.
The naked mole rat won’t win any beauty contests, but it could possibly win in the talent category. Its superpower: fighting the aging process to live several times longer than other animals its size, in a state of youthful vigor.
It’s believed that naked mole rats experience all the normal processes of wear and tear over their lifespan, but that they’re exceptionally good at repairing the damage from oxygen free radicals and the DNA errors that accumulate over time. Even though they possess genes that make them vulnerable to cancer, they rarely develop the disease, or any other age-related disease, for that matter. Naked mole rats are known to live for over 40 years without any signs of aging, whereas mice live on average about two years and are highly prone to cancer.
Now, these remarkable animals may be able to share their superpower with other species. In August, a study provided what may be the first proof-of-principle that genetic material transferred from one species can increase both longevity and healthspan in a recipient animal.
There are several theories to explain the naked mole rat’s longevity, but the one explored in the study, published in Nature, is based on the abundance of large-molecule high-molecular mass hyaluronic acid (HMM-HA).
A small molecule version of hyaluronic acid is commonly added to skin moisturizers and cosmetics that are marketed as ways to keep skin youthful, but this version, just applied to the skin, won’t have a dramatic anti-aging effect. The naked mole rat has an abundance of the much-larger molecule, HMM-HA, in the chemical-rich solution between cells throughout its body. But does the HMM-HA actually govern the extraordinary longevity and healthspan of the naked mole rat?
To answer this question, Dr. Vera Gorbunova, a professor of biology and oncology at the University of Rochester, and her team created a mouse model containing the naked mole rat gene hyaluronic acid synthase 2, or nmrHas2. It turned out that the mice receiving this gene during their early developmental stage also expressed HMM-HA.
The researchers found that the effects of the HMM-HA molecule in the mice were marked and diverse, exceeding the expectations of the study’s co-authors. High-molecular mass hyaluronic acid was more abundant in kidneys, muscles and other organs of the Has2 mice compared to control mice.
In addition, the altered mice had a much lower incidence of cancer. Seventy percent of the control mice eventually developed cancer, compared to only 57 percent of the altered mice, even after several techniques were used to induce the disease. The biggest difference occurred in the oldest mice, where the cancer incidence for the Has2 mice and the controls was 47 percent and 83 percent, respectively.
With regard to longevity, Has2 males increased their lifespan by more than 16 percent and the females added 9 percent. “Somehow the effect is much more pronounced in male mice, and we don’t have a perfect answer as to why,” says Dr. Gorbunova. Another improvement was in the healthspan of the altered mice: the number of years they spent in a state of relative youth. There’s a frailty index for mice, which includes body weight, mobility, grip strength, vision and hearing, in addition to overall conditions such as the health of the coat and body temperature. The Has2 mice scored lower in frailty than the controls by all measures. They also performed better in tests of locomotion and coordination, and in bone density.
Gorbunova’s results show that a gene artificially transferred from one species can have a beneficial effect on another species for longevity, something that had never been demonstrated before. This finding is “quite spectacular,” said Steven Austad, a biologist at the University of Alabama at Birmingham, who was not involved in the study.
Just as in lifespan, the effects in various organs and systems varied between the sexes, a common occurrence in longevity research, according to Austad, who authored the book Methuselah’s Zoo and specializes in the biological differences between species. “We have ten drugs that we can give to mice to make them live longer,” he says, “and all of them work better in one sex than in the other.” This suggests that more attention needs to be paid to the different effects of anti-aging strategies between the sexes, as well as gender differences in healthspan.
According to the study authors, the HMM-HA molecule delivered these benefits by reducing inflammation and senescence (cell dysfunction and death). The molecule also caused a variety of other benefits, including an upregulation of genes involved in the function of mitochondria, the powerhouses of the cells. These mechanisms are implicated in the aging process, and in human disease. In humans, virtually all noncommunicable diseases entail an acceleration of the aging process.
So, would the gene that creates HMM-HA have similar benefits for longevity in humans? “We think about these questions a lot,” Gorbunova says. “It’s been done by injections in certain patients, but it has a local effect in the treatment of organs affected by disease,” which could offer some benefits, she added.
“Mice are very short-lived and cancer-prone, and the effects are small,” says Steven Austad, a biologist at the University of Alabama at Birmingham. “But they did live longer and stay healthy longer, which is remarkable.”
As for a gene therapy to introduce the nmrHas2 gene into humans to obtain a global result, she’s skeptical because of the complexity involved. Gorbunova notes that there are potential dangers in introducing an animal gene into humans, such as immune responses or allergic reactions.
Austad is equally cautious about a gene therapy. “What this study says is that you can take something a species does well and transfer at least some of that into a new species. It opens up the way, but you may need to transfer six or eight or ten genes into a human” to get the large effect desired. Humans are much more complex and contain many more genes than mice, and all systems in a biological organism are intricately connected. One naked mole rat gene may not make a big difference when it interacts with human genes, metabolism and physiology.
Still, Austad thinks the possibilities are tantalizing. “Mice are very short-lived and cancer-prone, and the effects are small,” he says. “But they did live longer and stay healthy longer, which is remarkable.”
As for further research, says Austad, “The first place to look is the skin” to see if the nmrHas2 gene and the HMM-HA it produces can reduce the chance of cancer. Austad added that it would be straightforward to use the gene to try to prevent cancer in skin cells in a dish to see if it prevents cancer. It would not be hard to do. “We don’t know of any downsides to hyaluronic acid in skin, because it’s already used in skin products, and you could look at this fairly quickly.”
“Aging mechanisms evolved over a long time,” says Gorbunova, “so in aging there are multiple mechanisms working together that affect each other.” All of these processes could play a part and almost certainly differ from one species to the next.
“HMM-HA molecules are large, but we’re now looking for a small-molecule drug that would slow it’s breakdown,” she says. “And we’re looking for inhibitors, now being tested in mice, that would hinder the breakdown of hyaluronic acid.” Gorbunova has found a natural, plant-based product that acts as an inhibitor and could potentially be taken as a supplement. Ultimately, though, she thinks that drug development will be the safest and most effective approach to delivering HMM-HA for anti-aging.
A new study provides key insights in what causes Alzheimer's: a breakdown in the brain’s system for clearing waste.
In recent years, researchers of Alzheimer’s have made progress in figuring out the complex factors that lead to the disease. Yet, the root cause, or causes, of Alzheimer’s are still pretty much a mystery.
In fact, many people get Alzheimer’s even though they lack the gene variant we know can play a role in the disease. This is a critical knowledge gap for research to address because the vast majority of Alzheimer’s patients don’t have this variant.
A new study provides key insights into what’s causing the disease. The research, published in Nature Communications, points to a breakdown over time in the brain’s system for clearing waste, an issue that seems to happen in some people as they get older.
Michael Glickman, a biologist at Technion – Israel Institute of Technology, helped lead this research. I asked him to tell me about his approach to studying how this breakdown occurs in the brain, and how he tested a treatment that has potential to fix the problem at its earliest stages.
Dr. Michael Glickman is internationally renowned for his research on the ubiquitin-proteasome system (UPS), the brain's system for clearing the waste that is involved in diseases such as Huntington's, Alzheimer's, and Parkinson's. He is the head of the Lab for Protein Characterization in the Faculty of Biology at the Technion – Israel Institute of Technology. In the lab, Michael and his team focus on protein recycling and the ubiquitin-proteasome system, which protects against serious diseases like Alzheimer’s, Parkinson’s, cystic fibrosis, and diabetes. After earning his PhD at the University of California at Berkeley in 1994, Michael joined the Technion as a Senior Lecturer in 1998 and has served as a full professor since 2009.
Dr. Michael Glickman