Book Review—Why We Sleep: Unlocking the Power of Sleep and Dreams

Lying awake at three o’clock in the morning, I began silently cursing the pillow, the blankets, the streetlight filtering in through my window. I had never had trouble sleeping before, but a perfect storm of deadlines and responsibilities had made for several miserable nights in the past week.

It was around this time that I first stumbled upon Why We Sleep by UC Berkeley Professor Matthew Walker. I admit that I was primarily hoping for a quick fix for improving the quality of my sleep during stressful times. While I did learn a number of useful tips, I also received a host of terrifying statistics, anecdotes, and well-researched studies on the effects of sleep deprivation.

Why We Sleep undertakes an enormous task. Most people know that more exercise and a better diet are two of the easiest ways to improve one’s health. However, Walker argues that sleep is the third pillar of health—or even that the other two pillars actually rest on a foundation of a good night’s sleep. Walker sets out to convince the reader that a lack of sleep in this country causes, correlates with, or exacerbates nearly every disease and leads to enormous social and economic costs. At times, Walker’s tone borders on alarmist, yet he keeps the reader engaged with a self-aware tone and frequent breaks into lighthearted banter. Why We Sleep is also extensively referenced with numerous studies to support Walker’s points. By the end of the book, I found myself convinced by his argument.

Walker explains that lack of sleep can impact an impressive number of diseases, including Alzheimer’s, cancer, and cardiovascular disease. Sleep deprivation can also affect memory, learning, fertility, obesity, the immune system, and overall lifespan. In one passage, Walker compares the impairment of not sleeping for a night with the impairment of being drunk to the legal limit—a comparison supported by many convincing studies. In particular, Walker writes about a phenomenon called microsleep, where a person becomes unresponsive for only a second or two, which is long enough to cause serious damage while driving. After missing a night of sleep, the incidence of microsleeps increased over 400 percent compared to a group that slept eight hours. More concerningly, the same study found that participants who slept six hours per night for ten days also experienced a 400 percent increase in microsleeps. These results have remarkable health and safety implications for the many people who do not sleep the recommended seven to nine hours per night.

In addition to discussions about the effects of unhealthy sleeping habits, Walker provides fascinating insight into the evolutionary benefits and origins of sleep. For example, it is well-documented that teenagers’ body clocks naturally shift to be later than adults’. Walker proposes that this mechanism could have provided teenagers with time away from a watchful parental eye, facilitating the leap to independence. Similarly, a group of early humans that contained a mixture of early- and late-risers likely were far better protected from night predators and other nighttime dangers, since there were only a few hours when every person was asleep. Walker also notes that every animal ever documented experiences some kind of sleep, underscoring its evolutionary importance.

The main drawback to Why We Sleep is how hard it is to avoid the idea of taking a nap while reading this book. That’s right, I think to myself. I am sleep deprived! I should rest, just for a minute. Thankfully, the author strongly encourages this practice in the introduction, making my nap in the middle of chapter four entirely excusable. “I will take no offense,” he says to readers who fall asleep while reading his book. “On the contrary, I would be delighted.”

Article published via the Berkeley Science Review. Original story can be found here.

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Berkeley Science Review: From the Editor (Fall 2017, Issue 33)

The past year has been a whirlwind as Editor in Chief of the Berkeley Science Review. This is a reprint of my final From the Editor, which describes some of the work I’ve helped edit and produce over the past semester. The entire issue can be found here!

Dear Readers,

Autumn has arrived, with its crisp air and bustling streets. Sidewalks and coffee shops teem with students and researchers, chatting, exchanging ideas, and discussing science. In many ways, science is forged through these connections—between people, concepts, techniques—as ideas become woven together into true progress.

In this issue of the Berkeley Science Review, several authors uncover the connections that are central to scientific progress. Within these pages, find out how an on-campus program brings researchers together in “Breaking barriers”, and how international mentorship has sparked strong basic research programs in “World-wide science”. Explore how extreme life on our own planet connects to the study of life beyond Earth in “Life on the edge”, and how a paradigm shift in research results in better patient outcomes in “Ditching discovery”. This issue of the Berkeley Science Review also contains twin “From the Field” articles describing two very different kinds of research at UC Berkeley.

Each issue of the Berkeley Science Review is unique, shaped by the many writers, editors, designers, and photographers who invest  countless hours in its creation. I especially want to thank the design team, led by Art Director Ashley Truxal, for this bright and beautifully designed issue. I would also like to thank our managing editor, Katie Deets, who ensures that we continue to publish each new issue and grow as a student organization. I want to give special  acknowledgements to Nicole Haloupek, our blog Editor in Chief, and Dat Mai, our web director, for directing and expanding our online presence.

This is my last issue as Editor in Chief of the Berkeley Science Review. Being Editor in Chief has been one of the most challenging, rewarding, and surprising experiences I’ve had in graduate school. I have been fortunate to work with a talented and growing team of editors, writers, designers, and photographers. I am thrilled to introduce Dat Mai as the next Editor in Chief of the Berkeley Science Review. He is a talented third year graduate student in integrative biology, and he has acted as both an editor and web director for the Berkeley Science Review for the past several issues.

Enjoy Issue 33 of the Berkeley Science Review!


Emily Hartman

Editor in Chief

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Beyond the Controversy: How CRISPR/Cas9 Permanently Modified Molecular Biology

CRISPR/Cas9, a new, easy, and rapid genome editing technique, is at the center of heated debates over gene therapy, human embryo manipulation, and genetically-modified crops. While the most controversial applications of CRISPR/Cas9 likely will not affect the general public for years, this technique immediately and irreversibly changed the landscape of both basic and applied molecular biology research. Fast and easy genome editing is changing the way we think about disease models, drug development, and even organ transplantation.

The Beginning

Many people have written about the history of CRISPR/Cas9 in the last few years (here and here, to name a few). The story behind the discovery is fascinating, involving a yogurt company, virus-fighting bacteria, the plight of basic research, and cross-country patent wars.  Moreover, technology itself is controversial, mostly because it is much, much easier to use than other genome editing techniques.

So what makes CRISPR/Cas9 so much better—and more ethically ambiguous—than other genetic editing machines?

Before CRISPR/Cas9, if you wanted to alter a mouse’s genome—for example, if you wanted to make a mouse that will develop Huntington’s Disease—you would likely need to create protein machine that is designed to target a single position in a mouse’s genome. This was possible, but it took time, effort, and money.

Later on, say you decided that you instead wanted to study a different genetic disorder, targeting a new position in the mouse genome. Before CRISPR/Cas9, you would need to create an entirely new protein machine. This is because older genome editing technologies can’t easily switch to target new locations on a genome, and significant work was needed to accomplish any new genetic edit.

With CRISPR/Cas9, scientists can now use the same protein machine over and over again, customizing it to target any position on a genome. Making a new genetic edit became more like playing around with snap blocks and less like building a Lego set without instructions. Because of this, CRISPR/Cas9 has simplified and democratized genome editing, and the technology was rapidly adopted by labs across the world.

“The past two years has seen a nearly unprecedented acceleration and adaptation of a new biological technology,” said Kevin Doxzen, a UC Berkeley Biophysics graduate student, to The Berkeley Graduate. Doxzen works for Professor Jennifer Doudna, who co-discovered CRISPR/Cas9 with several others. “The combined simplicity and efficacy of CRISPR-Cas9 creates an endless spectrum of applications.”

These applications include several controversial ones that consistently dominate news headlines. However, CRISPR/Cas9 has also altered molecular biology in more subtle ways.

Modeling disease

In the past hundred years, scientists have used mice to study an enormous number of diseases. While early studies involved breeding mice for traits of interest, more recent technology allowed researchers to study mice with genetic mutations. The 2007 Nobel Prize in Physiology was awarded to the scientists who developed ways to genetically manipulate small mammals, including mice. However, this technique has limitations. For example, it doesn’t work well with larger mammals, and it’s challenging to create multiple genetic edits.

Ultimately, while mice are an invaluable model system, humans are far more complex organisms. Some researchers argue our reliance on mice is part of why so many promising drug treatments fail when tested in humans. Recently, scientists have begun using CRIPSR/Cas9 to create more complex animal models of disease—including models in larger organisms such as pigs and sheep.

Last January, a team of researchers in China published a study where pigs were modified with CRISPR/Cas9 to contained mutations associated with Parkinson’s Disease. Other studies have generated large animal models of Alzheimer’s, Huntington’s, and ALS (Lou Gehrig’s Disease). Scientists hope that these models will provide more accurate models of these complex diseases, enabling better drugs and a better understanding of how these diseases progress.

Which piece matters?

In recent months, Zika virus has developed into a significant public health concern, prompting a flurry of effort to develop preventative vaccines or curative therapies. The Zika virus has only been minimally studied, and until recently researchers had few leads on how to develop new drugs.

Scientists from the University of Massachusetts worked to identify which pieces of a human cell necessary for the Zika virus to successfully infect and kill it. Like most viruses, Zika co-opts cellular machinery from its host cells—so identifying which host proteins are required for infection is key to developing new and effective drugs.

The researchers used CRISPR/Cas9 to systematically delete genes from a human cell line. The cells were then infected with Zika virus. At the end of 8 days, 95% of the modified cells had died. However, a lonely 5% survived and were sequenced. These survivors likely contained CRISPR/Cas9-mediated deletions that helped them survive the virus—meaning, Zika might require those genes to survive and proliferate. This study gave the scientific community a list of leads on how to develop new Zika therapies.

“These genetic screens give us our first look at what these viruses need to survive,” said Dr. Brass, lead author on the study, in a press release. He emphasized that the CRISPR/Cas9 screen could be used to study other emerging viral threats. “We plugged Zika virus into our system and immediately began studying it.”

Humanize organs

GMO pigs

Genetically modified pigs may provide scientists with better models of human disease. Flickr, credit thornypup.

Over a hundred thousand people are currently on the waiting list to receive a new organ. Pig organs, which are similar in size and shape to human organs, have long been studied as a possible alternative to human organ transplantation. However, pig organs contain a health hazard encoded in their genomes: porcine viral DNA, often dormant, can cause viral infections in humans. Because some of these pig viruses can infect humans, pig-to-human transplants are dangerous to the recipient.

Last year, scientists from Harvard snipped away 62 instances of pig viral DNA from a pig kidney cell line with a single CRISPR/Cas9 protein machine. These pieces of viral DNA were very similar—so similar, in fact, that one pair of molecular scissors effectively removed all unwanted DNA in one pass. This “cleansed” cell line effectively prevented viral infection and transmission to human cell lines. While this technology has yet to be tested in the (far) more complex pig animal, this incredible study brings a new angle to xenotransplantation.

The future

It will likely be many years before CRISPR/Cas9 is used to treat cancer, or to edit viable human embryos. Despite the advantages of CRISPR/CAS9 in molecular biology research, there’s a significant gap between using a tool in a lab, and using it on a human. These molecular scissors would have to cut precisely, 100% of the time, with no mistakes, before they can be used on humans.

Take, for example, the idea that we can use CRISPR/Cas9 to edit human embryos. In reality, to edit a human embryo requires utter precision—you need to be able to change the genome in exactly one place, no more no less. This level of precision is challenging in biology. “Scientists are still trying to make Cas9 as precise as possible in order to prevent any “off-target” effects,” said Doxzen, “but some error is unavoidable in noisy biological systems.”

The precision, reproducibility, and control of CRISPR/Cas9 must reach an entirely new plane before we start envisioning a Gattaca-like future. Still, even today the technology has altered molecular biology forever, enabling studies that seemed impossible only a few years ago.

Title Image: Flickr, credit NIH Image Gallery. The CRISPR/Cas9 protein machine, pictured here, acts as molecular scissors, snipping double stranded DNA in a genome.

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The business of microbiology

Last night, Bill Gates spoke to a thousands of scientists at the opening night of the American Society for Microbiology conference. Over an hour, he discussed past and current work on various diseases including polio, malaria, tuberculosis, and others.

In each case, Gates’ language and perspective were far more financial than a typical keynote speech. Gates didn’t wonder how we can save a single life; he wondered how we can save the most lives possible with a limited number of dollars. Which disease is most cost-effective to target. And ultimately, how we can save a life for under $1000. “A little bit of investment done properly is catalytic,” Gates said.


Flickr, Credit United States Mission Geneva. Photo taken at Meeting organized by Bill and Melinda Gates Foundation at the WHO in 2011.

The language of cost effectiveness changed, when discussing eradication, though the emphasis on tracking outcomes per dollar was still clear. “Zero is a magic number,” Gates said, because future intervention costs are eliminated. While the last 1%, or 0.1%, of a disease is the most difficult to eliminate, it may also be the most important. Using polio as an example, he showed how 400,000 cases in 1985 has dropped to 16 so far in 2016—though the magic number still remains elusive, due largely to politics, instability, and infrastructure. Looking forward, Gates identified malaria and poor nutrition as global health problems that could be solved for under $1000 per life.

Hearing Bill Gates discuss the nuances of microbiology from a business perspective was eye-opening. I appreciated the focus on effective change per dollar, and on tracking “success metrics”. Patience is still necessary in research, yet hearing speakers like Gates inspires me to think beyond the day-to-day of academia.

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Editing sensationalism (or: Don’t throw away your cellphone)

Earlier this week, a top story on my Google News feed caught my eye. “Report claims cellphones cause cancer!” one site blared. “Mobile phones can cause cancer,” read another headline. One was particularly bad: from the headline, to the buried critiques, to the opening sentence (“It’s the moment we’ve all been dreading.”)

I immediately sigh: it seemed highly unlikely to me that the study, whatever it said, would say that cellphones definitely cause cancer.

Out of morbid curiosity, I pulled up the original article. Even the title—bland, like most scientific articles—immediately contained a clear and obvious caveat: “Report of Partial Findings from the…Carcinogenesis Studies of Cell Phone Radiofrequency Radiation…” (emphasis mine). Partial findings! The study wasn’t even fully released yet. I scrolled down, noting that the pdf actually contained reviewer comments, a practice that is not overly common in my field. I liked it. It allowed me to immediately hear what other experts thought of the article. Generally, the reviewers were cautious. Every review contained a criticism, some harsher than others.


Credit: Steve Paine on Flickr

Others have already written about why this study does not prove that cell phones cause cancer, or why we shouldn’t immediately stop using our phones. The short version is that there were some concerns about the control group, and the statistical significance was weak—meaning the positive result (ie cellphones cause cancer in rats) may be false, even though it seems true given the data. Male rats and female rats did not produce the same results. Studies done in rats don’t always translate to humans. And of course, you should never trust a single study anyways. Maybe the most obvious argument against the headlines is that we’ve been using cell phones for years without a huge increases in brain cancer, and that many other studies do not agree with these finding.

Sensationalization has real consequences for science and scientists. Articles like these lead John Oliver to tear apart my field on HBO, correctly identifying sensationalization as a reason why the public no longer trusts science news.

To be clear, this doesn’t mean the study wasn’t well done, or important. It just means that cellphones may or may not cause cancer. Science moves slowly, and this is one study among many on the effect of cellphones.

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Chimpanzees, Top Hats, and Biomedical Research

I’d heard a lot about Emma before I finally met her. I’d heard about her resourceful, clear nonverbal communication, where she seemed to use magazine pictures or toys to get her point across. I’d heard that her games were playful and varied, and her social network intricate.

Emma was a chimpanzee, living in the National Chimpanzee Sanctuary in Louisiana. I met her when I visited my friend and chimpanzee caretaker last April. As we approached her room, she wandered over, obviously interested in the unfamiliar faces. We began playing a game, asking Emma to touch parts of her face—her eyes, her ears, her mouth. To my surprise, Emma played along, easily keeping pace with our requests.

Of course, decades of scientific research should’ve prepared me for the similarities between humans and chimpanzees. These nonhuman primates are our closest evolutionary neighbors, and we share 98% of our genome. Chimpanzees are socially adept, creatively use tools, and can communicate with sign language, gestures, and verbal calls. In fact, chimpanzees are thought to have better short term memory than humans, and are better at simple games of random chance like rock, paper, scissors. Both of these skills, and others, are likely products of their own unique evolutionary history.

2533137267_891faf6259_oGiven their unique intelligence and similarities to humans, it is unsurprising that the National Institute of Health decided to end its use of chimpanzees in medical research last yaer. Around 310 government-owned chimpanzees are to retire. The NIH is largely taking its lead from the Institute of Medicine, which declared in 2011 that chimpanzee research could no longer be justified. Alternative animal models and noninvasive computational approaches reduce the need to experiment on our closest living relative, according to the report.

In addition, until recently chimpanzees in the wild were classified endangered, while their relatives in captivity were listed as threatened. This distinction, or “split listing”, allowed scientists and entertainers to skirt strict breeding regulations and perpetuated using chimps in entertainment. This has significant effects on the chimpanzee conservation efforta study published in 2011 shows that subjects who see chimpanzees in commercials have a skewed perception of how endangered chimps are (very).

While these policy changes are important steps for chimpanzee conservation, more needs to be done. With only a few hundred thousand chimps left, now is the time to support efforts to slow deforestation, be an informed consumer, and learn more about one of our most intelligent cousins.

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Protecting gut bacteria: Targeted antibiotics reduce microbiome disruption in mice

Broad-spectrum antibiotics, commonly prescribed for many kinds of bacterial infections, are one of the great medical triumphs of our time. Before antibiotics, scientists had few tools to fight diseases that had affected humans for centuries; now, we can simply swallow an oral pill to fight off once-lethal infection within days. Penicillin alone is estimated to have saved up to 200 million lives since its discovery.

Still, taking antibiotics is not fun, and many people experience unpleasant side effects. In more serious cases, opportunistic secondary infections, such as C. difficult or C. albicans (yeast) can take root following antibiotic treatment. These side effects largely stem from the fact that antibiotics target and kill pathogenic bacteria as well as naturally-occurring bacteria. Today, as we begin to learn more about the importance of a healthy microbiome—bacteria that naturally occurs in our gut and elsewhere—researchers are now looking for a new, more selective kind of antibiotic.


Credit: mostly*harmless, flickr

This week, scientists from St Jude published a study that takes a small step towards selective antibiotics. Published in Antimicrobial Agents and Chemotherapythe researchers track how a targeted antibiotic—one that selectively inhibits a protein found in only a few bacterial species, including Staphylococcus aureus—altered the gut microbiome of mice in a 10-day treatment. Control mice received broad-spectrum antibiotics or an inactive agent.

At the end of ten days, mice that received the selective antibiotic had a gut microbiome that seemed largely unchanged. In contrast, the gut microbiota showed far reduced bacterial abundance and diversity in mice that received broad-spectrum antibiotics.

While these results are promising, it is important to note the limited sample size (only five mice were used per condition). Additionally, it remains to be seen how these results will translate to human subjects. Full text of this article can be found here.

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