Natural Selections interviews Ali Brivanlou, Principal Investigator Laboratory of Stem Cell Biology and Molecular Embryology, the Rockefeller University.
Together with his team, Ali investigates the molecular pathways underlying cell communication during development. Notably, his team was recently able to preserve human embryos in culture for up to 14 days. This revolutionary achievement will illuminate unknown information about our own origins that may be crucial to understanding and reversing neurodegenerative diseases, repairing diseased tissues, and growing human organs in vitro.
NS: What differentiates a stem cell from any other cell type?
AB: Stem cells come in different flavors: embryonic stem cells (ESCs) and adult stem cells (ASCs). The former are derived from the early embryo, a few days after fertilization, while adult stem cells are continuously present in almost all tissues of our body, and allow for regeneration. The big difference between these two groups is their range of ability. A human or a mouse ESC can give rise to all the organs of the body. As time moves forward, their potential decreases. So, i.e., an adult hematopoietic stem cell can only give rise to blood derivatives, and bone stem cells will give rise to bone. This difference is intense, because ESCs are the only cells that can mimic a fertilized egg and give rise to a whole organism. They contain all the information sufficient and necessary to create all the organs and their organization. These are very unique properties that put ESCs on top of the hierarchy of decision-making that allows all the fates to be established. This is really exciting because we can use human stem cells in clinical settings to repair or replace tissues; and also because it teaches us, at the most fundamental level, how cell fate is established.
NS: What gives a stem cell the information to form a whole individual?
AB: This is a very old biological problem. About 2,300 years ago, Aristotle described the development of a bird inside an egg and created the foundation of current embryology. At the end of the 19th century and beginning of the 20th there were two schools of theories. One defined by the British school of embryology, suggesting that fate is based on lineage – you know who you are based on who your parents and grandparents are. The other is the American school, suggesting that [it] is not the lineage that determines your fate, but your neighborhood – you know who you are depending on where you end up being and who your neighbors are. It ends up that the American school was correct, not the British. Fate in an embryo is determined by where a cell finds herself. I figured out that this is mediated by cell-cell communication, cells have a dialogue. As the embryo grows and the number of cells increases, their neighborhood becomes more complex and their fate more refined. This is mediated by receptors and secreted factors. Ligands come out of the cells and bind receptors in the recipient cell that sends the signal to the nucleus. An extrinsic piece of information becomes an intrinsic response in transcription. This allows cells to gradually figure out what they will be. We learned their language and how to manipulate it to change their fate. Many people in the stem cell field are interested in the applications of this knowledge. I am still interested in learning more about this communication.
When I was a graduate student at Berkeley and during my postdoc at Harvard, it was still questionable whether the American school was right. So I asked, “If the neighborhood defines your fate, what kind of fate would you have if you don’t have any neighbors?” Cell communication as a fate determination mechanism is conserved over millions of years. So, I took a frog embryo, which is a ball of 2,000 cells, and I dissociated them so they could no longer communicate. Any ligand sent was diluted to infinity in the medium so other cells could not “hear” it. The result was very surprising. All embryonic cells: those going to become gut, or kidney, liver, muscle, bone; every single one converted to a brain cell. Not receiving any signals pushes a cell towards a brain fate. This was very controversial when I published it because one thinks that this is the most sophisticated organ, but how can this sophistication arise from zero communication? At some point, a group of cells in the embryo decide to no longer listen to their neighbors. They close all communications and give rise to the dorsal anterior part of the nervous system. In order to generate other fates, cells have to say “Do not close your windows or your doors, listen”. This complexity is something I’m still trying to dissect.
NS: Before it was possible to obtain embryonic stem cells only from embryos. Now they can be taken from different tissues. How is this done?
AB: In 2012, a Nobel Prize was given to two of my heroes: John Gurdon and Shinya Yamanaka. They showed different things with a common denominator: that biological time can go backwards. Yamanaka showed that any adult cell can be reprogrammed to behave like an ESC. John Gurdon, who mentored both my postdoc and graduate student advisor, was the first to clone an animal. He showed that [it] is possible to create a whole individual from the nucleus of a skin cell of a tadpole (that is ahead in time) placed in an egg. But it took more than 50 years to recognize John Gurdon for his contribution. If you ask people which one was the first animal to be cloned, they always say Dolly, never the frog. But Dolly was cloned decades after the frog, people didn’t care the same. It was only when it got closer to humans that people started to really get interested.
NS: Usually embryos are implanted in women about one week after fertilization. Before you were able to keep embryos in culture for 14 days, nothing was known about this second week of development. What are the potential implications of these discoveries?
AB: It has tremendous implications. Mammalian development post implantation has always remained a mystery. The architecture and geometry of the embryo changes as it attaches to the walls of the uterus and it becomes invisible. We showed what happens after implantation in humans, unveiling, for the first time, our own origins. This was spectacular and unexpected because we showed that the human embryo has all the information to sustain its development at least for 14 days in the absence of maternal inputs. It was mesmerizing to see that self-organization occurs in the embryo, cells decide their fate and they organize in a specific structure of concentric circles, generating waveforms from the center to the edge. We stopped at 14 days because there’s a guideline in the United States, called the 14-day rule.
NS: If there was a reevaluation of the 14-day rule, where would you set the new limit and why?
AB: We are in discussions with the National Academy of Science, the National Academy of Medicine and the National Academy of Bioengineering. A lot of this work is done in collaboration with my physics colleague Eric Siggia from RU. We are trying to answer questions like “Do we want to move further than 14 days?” If the answer is yes, “How far do we want to go?”.
I’m very happy and proud to initiate the debate so we can create a dialogue regardless of our background, culture, language, or religion and together discuss how the new technology available can [help us] reevaluate this rule. This is a great question and the debate will resolve by itself. My personal opinion is that if we can double the 14 days, if the embryo survives, that would be a great advance for the 21st century, and we could get important information about organ formation, or organogenesis, because it happens during this time window.
NS: How far are you from creating human organs from stem cells?
AB: Very close actually. This work is in review in Nature now. Once you can make a human embryo, the mother of all the organs, you can make organs by [the] hundreds. If you know the language being used among cells to distinguish fate, then I can assure you, it’s a matter of [a] short term.
NS: What other passion do you share with science?
AB: The passion of curiosity, pushing the boundaries of the limit of what’s beyond. This is a human tradition, from Christopher Columbus wanting to see what is on the other side, to the pioneers of the West Coast wanting to see the boundaries of the land. It’s a natural phenomenon in us, to be attracted to the unknown. When I look down that microscope, my eyes send signals to my brain that tell me, “I want to know where I come from.” Where does that need derive from? That need of self-understanding, I think is very human. What drives it? I don’t know, but for me it’s a necessity, not a choice. I need to know, I don’t know why, but I need to know.
“My disabilities have not been a significant handicap in my field, which is theoretical physics. Indeed, they have helped me in a way by shielding me from lecturing and administrative work that I would otherwise have been involved in. I have managed, however, only because of the large amount of help I have received from my wife, children, colleagues, and students. I find that people in general are very ready to help, but you should encourage them to feel that their efforts to aid you are worthwhile by doing as well as you possibly can.”
Morocco Log #1
Stepping straight onto the tarmac of Casablanca Mohammed V International Airport after a 6 hour flight with the Royal Air Morocco, I am officially on the continent of Africa!
The reputation of Casablanca would be overrated if it were not for the magnificent Hassan II Mosque by the Atlantic Ocean. Marrakesh, on the other hand, is what I imagined Morocco would be like – vibrant colors, ancient history, and exotic culture blended with chaos everywhere. Djema Square at the heart of the old medina is the biggest outdoor marketplace in Marrakesh. Every day, when the sky dims into a scarlet sunset and the square is re-lit with a sea of tent light bulbs, when the delicious smell of BBQ travels to your nose through clouds of smoke that rise above vender stalls, when the boisterous crowd and circus animals pour into the square from all directions, you can’t help but realize that this place has just woken up and the show is about to begin.
Ainhoa Perez Garijo
“Hokusai’s Great Wave” by Bonnie Monteleone, 2016
Greenepeace USA, Turtle and Plastic in the Ocean © Troy Mayne / Oceanic Imagery Publications
Nine years ago Ainhoa Perez Garijo took the first steps towards reducing her waste and today she and her family live almost completely waste-free, meaning they do not use any unnecessary plastics and try not to not send anything to a landfill. When Ainhoa first moved to New York City almost ten years ago she became aware of the massive amount of waste that the city produces every day. The waste suddenly became “visible” to her as she realized she “was coming back from shopping with more plastic and packaging than food.” Although her transition to zero-waste was a slow process, she thinks that she could have done it more quickly and hopes that she is at the forefront of a movement that will pave the way for others.
Ainhoa grew up in the large metropolis of Madrid, Spain, and always cared about both animals and nature. Most people that she knows who live zero-waste grew up “close to nature, in the middle of the mountains, or close to the ocean,” but that was not the case for her, and she loves living in big cities and enjoying all that cities have to offer. Being environmentally aware and living in a city do not have to be mutually exclusive.
Ainhoa is currently a post-doctoral associate in Herman Stellar’s lab where she studies the “last will of dying cells,” or how cells undergoing apoptosis communicate with neighboring cells in order to coordinate collective cell death. You may recognize her from her involvement in the Child and Family Center on the Rockefeller University’s campus. A mother of two daughters, she believes that her kids have been extremely helpful in her path to zero-waste. As she says, “It’s really funny to see how my older daughter is aware of plastics and reminds her dad when he forgets to refuse any plastic item.” Ainhoa is also passionate about teaching and is currently part of the Scientist-in-Residence program, a NYC-wide initiative that matches scientists with classrooms in the NYC area to bring scientific research and expertise to high-need schools.
This past year, Ainhoa partnered with Rockefeller’s Science Communication and Media group to launch the Science & Nature documentary series, featuring various documentaries about the environment, each followed by a discussion about how to promote more sustainable practices on campus. Ainhoa wants to inspire the campus using documentaries similar to those that challenged her to change her daily life and become aware of the issues that we as a community have the opportunity to tackle. So far, Ainhoa has shown two documentaries in the year-long series, and this initiative has already brought together many people who have offered some great suggestions about how we can improve sustainability here at Rockefeller. She has plans to meet with the Sustainability Committee to relay these suggestions and to work with the administration on reducing unnecessary waste.
Ainhoa believes that whereas “Rockefeller is such a special place, probably the best institution to do research in the world…with the best scientists, the best campus, the best programs, and the best standards of living…we should become leaders in environmental policies as well, especially considering the current political situation.” As she emphatically exclaims, “If scientists don’t lead this movement, who will?” She hopes to help others in her community start to see waste. Once we realize how much trash we throw away every day and understand that it is mostly unnecessary, she declares that “it’s actually quite liberating.”
Plastic pollution is an environmental issue that largely affects CO2 emissions and conservation of biodiversity. Today, the Rockefeller community should start working with companies that use less packaging and efficiently reuse and recycle materials. Our cafeterias on campus should also be plastic-free, as there are “plenty of zero-waste options.” It is time to change our lifestyles because we are damaging the environment beyond repair. This does not only affect other species and the planet, but also greatly impacts humankind and our children. As Ainhoa pronounces, “We can easily live without plastic, or without fossil fuels, but we cannot live without breathing.”
Ainhoa believes that just as with other movements in the campaign for human rights, it is now time for the environmental movement. Although change may be initially regarded as “crazy, idealistic, or simply impossible to accomplish…once the shift is made, younger generations cannot even believe that things were the way they were in the past. We could call this the Planet Rights Movement. And Rockefeller University could make history and be remembered as a leader in this movement. It’s just the right thing to do.”
As she said passionately during her introduction to the last documentary, “As scientists, shouldn’t we do what science has told us is right and reduce our impact on our environment…People think that I am crazy and ask me how I could go waste-free…and you know what I tell them – it’s actually very easy.” If anyone is interested, she is happy to help them along the way. She wants you to get in touch, and here she has shared some of her tips for beginning your transition to zero-waste today.
Ainhoa’s Tips to More Sustainable Living:
- Study your garbage and try to think of alternatives to what you throw away. One day go to the supermarket and challenge yourself to buy everything plastic-free. It will help you start “seeing” the plastic.
- Refuse single-use plastics, especially the big 4: plastic bags, plastic bottles, plastic cups, and plastic straws. There are reusable alternatives for each of these items that you can carry with you every day.
- Food waste makes most of the trash that is generated in most households. If you live in Faculty House/Scholars Residence, there is compost collection in the basement. Otherwise you can take your food scraps to Green Markets or even have your own composting bin at home. Make sure that you don’t buy food in excess, and make sure you cook it, eat it. or freeze it before it goes bad.
- Take your own containers to stores. This is probably the easiest and most efficient way of reducing your plastic waste. The best places to buy things in bulk are food co-ops. I like very much the 4th St. Co-op and the Bushwick Co-op. You can also find large bulk food sections at Whole Foods and Fairway, buy meats and cheeses at deli counters in supermarkets where they are not pre-wrapped, and buy laundry detergents and soaps at the Package Free Shop in Brooklyn. You can find many more options using the Bulk app.
- Look for plastic-free alternatives or make your own. For example, I buy milk in returnable glass bottles from Trickling Springs Farms, make my own yogurt, ice cream, and toothpaste, and use a compostable toothbrush made of bamboo. For feminine products, switch to the menstrual cup or reusable panty liners, and with kids use reusable cloth diapers. And as a general rule, if there is something you want and can’t find package-free in stores, look for a way of making your own. There are plenty of easy recipes online for everything!
- Get rid of your trash can. Once you manage to greatly reduce your garbage, this is the best way to get as close to zero-waste as possible. Collect your remaining trash in a cup or jar in the kitchen counter, and throw it in a trash can in the street when you need to. This will make you much more aware of everything you dispose of. And it also means you won’t use plastic bags for the garbage!
- Repair, repurpose, or donate. Fix your non-working items, sew your broken clothes, be imaginative and make with them something new, or use something else you already have to replace them. If you want to get rid of something, think of donating instead of throwing it away. For unusable clothes and shoes, a good alternative are the Fabric Recycling points in most of the NYC Green Markets. They’ll use them to make insulating material.
- The single most effective way of not producing waste is not buying! Every time that you want to buy something ask yourself: do I REALLY need this? If you really need to buy, then buy second hand and products made from natural materials and with minimal or no packaging. The best of all: get it in the Faculty House Thrift Shop where it will be almost free and the few dollars you spend will benefit the RU kids. If you want to buy something new, some good options are the Package Free shop or the online store Life Without Plastic. If you want to buy a gift for someone else think of experiences instead of material things such as tickets for a museum, theater, opera, an online gift card for a bakery, restaurant, or spa, a cooking, music, or dancing lesson, etc. The options are innumerable and the gifts are way cooler.
- Recycling should be the last resource, only when you have something that you couldn’t refuse, reduce, or reuse. Even though it’s better than sending something to landfills, it still takes lots of energy and carbon emissions to transport and recycle something (not to mention that collection involves tons of plastic bags). Additionally, plastic recycling is especially problematic and, contrary to glass or aluminum, it is usually “downcycled” into less desirable products that can no longer be recycled. So try to make every effort to avoid plastic, even recyclable ones.
adjective \ ˈgrēn \
1. of the color green
2. covered by green growth or foliage • green fields
3a. often capitalized relating to or being an environmentalist political movement
3b. concerned with or supporting environmentalism • green consumers who practice recycling
3c. tending to preserve environmental quality (as by being recyclable, biodegradable, or nonpolluting) • greener energy solutions
The word “green” has always been infused with life: according to the Online Etymology Dictionary, its origins, circa the early thirteenth century, are Old High German, stemming from the word gruoni (“to grow,” specifically in reference to plants and grass). Gruoni went on to influence Old English grene and Northumbrian groene, meaning “green, the color of living plants,” or, in reference to plants, “growing, living, vigorous.”
For roughly 700 years, “green’s” definition has not veered too far from its source. The word as it exists today has over ten definitions (though I have only focused on three), and they all relate back to the natural world somehow. Take, for example, the definition meaning “not fully qualified for or experienced in a particular function,” or “deficient in training, knowledge, or experience” (i.e., a green recruit). Perhaps the connection to nature is not immediately obvious, but when considering one of green’s other definitions—“not ripened or matured,” or “fresh, new”—it becomes clearer. There is something appealing and perhaps a bit magical about a word that was borne of observing and describing nature in its innate state: growing, living, and vigorous.
In the twentieth century, “green” began to shift into a decidedly more political word, wherein humans moved from observing nature to taking an active part in its protection and preservation. Earth Day was first celebrated in 1970, and, a year later, the organization Greenpeace was founded for the purpose of, according to their website, “expos[ing] global environmental problems and promot[ing] solutions that are essential to a green and peaceful future.” Although Greenpeace has been a source of controversy and criticism, both it and Earth Day exemplify the third definition of “green,” which means “relating to or being an environmentalist political movement,” or “concerned with or supporting environmentalism.” The Green political movement has spanned nearly fifty years since its inception (in the United States, environmental protection has been a key issue for closer to one hundred years; the word green has simply come into play more recently). This movement spans strategies and scales, from direct anarchist actions to the outgrowth of green roofs in urban centers to individual efforts to compost. The connection to nature is still direct and explicit in this last definition, but the key difference is our own agency; in order to keep nature growing, living, and vigorous, we now have a responsibility to respect and protect it.
My Thoughts On Two Documentaries: Long Strange Trip (Amazon Studios, 2017) and Eric Clapton: Life in 12 Bars (2017 film; released on Showtime Network in February 2018 for television)
Cream in the 1960s, (from left to right) Ginger Baker, Jack Bruce and Eric Clapton (source: Wikipedia)
Promotional poster for Long Strange Trip (Amazon Video)
Two recent documentaries, one on the Grateful Dead and the other about Eric Clapton, offer fantastic insights into two of the most talented and powerful musical forces that arose in the 1960s. All of the surviving members of the Dead are interviewed at length in the Amazon Studios-produced the 6-part, Long Strange Trip directed by Amir Bar-Lev. Eric Clapton cooperated with director Lili Fini Zanuck in the making of the story of his life by giving voiceover narration to archival film footage, music, and documents from his long career as a premier English blues and rock guitarist. Both documentaries offer incredible journeys into the music and lives of those involved, including candid appraisals of some of their darker moments. In particular, the living-on-the-edge life of the Grateful Dead’s late leader Jerry Garcia (1942-1995), his tragic death, and the terrible self-abusive states of addiction suffered by Clapton.
I saw the Grateful Dead three times between 1978 and 1980. During that period, I would often play along at home or college on guitar with Dead albums, where I learned to listen carefully to the other players and respect the unity of the whole sound rather than standing out as a soloist or “stepping” on another musician’s phrase. The Grateful Dead were known for playing as a unit and for being uncannily of one mind during their complicated and experimental live performances. When I joined a band in 1979, I took this lesson to heart as I played with my fellow bandmates. In the documentary, bassist Phil Lesh, drummers Mickey Hart and Bill Kreutzmann, and rhythm guitarist and vocalist Bob Weir delight in discussing the magic of playing and jamming live and how the audience would be taken along with them on their journey.
As the Dead’s audience grew, it made a transition from arena performances to stadium venues. These shows attracted a large number of people who would arrive without tickets, many in hope of gaining free entry by slipping through fences or gates. Others would set up booths to sell unauthorized merchandise and there were those who abusively drank alcohol or ingested drugs leading to erratic or often dangerous behavior. The members of the Dead grew alarmed as violence became a regular feature in stadium parking lots, at times to the point of loss of life. Lesh, Weir, Hart and Kreutzmann took to recording public service announcements with forceful messages that only ticket holders were welcome and that the circus-like atmosphere that had been created was not in the true spirit of what the band stood for.
The surviving members of the Dead appear to have emerged in excellent mental shape after years of substance abuse and come across as sharp, insightful and articulate in the film’s interviews. Lesh gives a detailed account of how virtuoso guitarist Garcia deteriorated from heroin use in his final years. He notes that even if the band had stopped touring as an intervention, Garcia would have likely just gone out on the road with his solo band and met with the same sad end.
The musical soundtrack of Long Strange Trip confirms that the Grateful Dead’s performances remain beautifully textured and vital, with each member playing lines of melody that unite seamlessly into a magical whole for a refined essence.
Eric Clapton: Life in 12 Bars is a completely different tale of self-destructive behavior of a guitar magician. The documentary runs just over two hours and is an extremely painful two hours at that.
I have seen Clapton perform many times, but not in the past 25 years. I have great memories of a concert in the 1980s at a small club in Manhattan and of an outdoor festival in 1978 at an aerodrome field outside of London. I became aware of the talented blues player in 1968 when my brother mixed up our daily album selections with records by a far out band from England called Cream. I was 11 years old and records such as Wheels of Fire completely changed my understanding about music. Cream’s extended jams pounded at a breakneck pace, with Mr. Clapton soloing at blistering speed amid the complex, jazz-inspired drumming of Ginger Baker and the wandering, fuzzed basslines of Jack Bruce. I believe that this was Mr. Clapton’s peak period which was matched in 2005 at Cream’s reunion concerts at the Royal Albert Hall and Madison Square Garden where the wisdom of all of his playing years coalesced.
The band’s final album, Goodbye, was a farewell to their fans offering a selection of live recordings and studio songs. The opening number is a live version of a fast-paced blues song that was one of their signature numbers, “I’m So Glad.” The song has Clapton tearing off what I believe to be the finest guitar solo in all of rock music, performed with screaming passion and intensity that never flags.
The Cream years were rough on Clapton, having already emerged as a blues star and given the nickname “God” by his London fans. Whereas the Dead welcomed widespread fame, Clapton didn’t care in the least about stardom. He wanted to perfect his craft and was on a mission to educate the world about the unrecognized African American pioneers of the blues genre. The late Muddy Waters and B.B. King appear in the documentary speaking fondly of the unexpected popularity of their music after Clapton had worked tirelessly to promote it.
In one film segment from the 1960s, Mr. Clapton plays some riffs for an interviewer and notes how he can be “aggressive” as he slashes into a searing lead. This particular guitar tone had been a Cream staple sound during live performances, for example, in “Deserted Cities of the Heart”. Later in the film, as we watch Mr. Clapton descend into years of alcoholism, he goes on record at the time as hoping his life would end, in order to remedy his suffering. In one interview, his eyes barely open, he bitterly wishes that Cream had never existed and says that he loathed, once again, his “aggressive” tone and playing from that time.
Clapton describes in detail how his problems stem from his troubled family history, having grown up believing his grandmother and step-grandfather were his parents only to learn his older sister was his mother and that his father was nowhere in the picture. His mother went off to have another family, and when he finally does meet with her, she acts terribly, scarring him for life and pushing him into the solitude of obsessive practice, which made for a genius guitarist. Equally tragic is how much Clapton enjoyed the positive energy and friendship of fellow blues genius Jimi Hendrix and how much the overdose death of Hendrix left him feeling isolated and alone with his talents and musical insights.
I had known of Clapton’s heroin addiction, which ceased in the 1970s, and that he’d gone into alcohol rehab years later. I had not known until 12 Bars that his drug and alcohol abuse spanned decades of seemingly nonstop misery. There were years lost fretting over his relationship with Pattie Boyd, the ex-wife of his close friend, George Harrison of the Beatles. She had inspired the tortured song “Layla”, which remains a fantastic piece of music. Viewers of the film learn just how long his infatuation with Boyd lasted before it came to a maddening culmination and how Clapton remained unhappy despite finally winning her over.
The bulk of 12 Bars focuses on the period of Clapton’s emergence as a Blues guitarist through the “Layla” sessions. Many of his solo studio albums are dismissed as uneven and uninspired. After years of playing drunk onstage and making angry, embarrassing statements to his audience, he regained the great magic of his live concerts. There is a concert film produced in 2002, One More Car, One More Rider where he shines on acoustic guitar during “Bell Bottom Blues” with the late Billy Preston riffing beautifully on the organ. Clapton was also the band leader of a fantastic musical celebration of the life of the late George Harrison in 2002, “The Concert for George”, which recently was re-released in selected theaters.
12 Bars ends in the present with Clapton happily married and enjoying life with his children. He operates and funds an alcohol rehab center to assist those in need. He is set to perform concerts in October at Madison Square Garden. We can only hope that he has truly finally found peace of mind. And whether I am misinterpreting his guitar tone or not, I’ll always have the music of Cream and many other songs by Clapton to simply enjoy and assist me in my own personal journey in this life of the heart and mind.
“A flurry of leaves at the window
like those calendar pages flying
in old movies
to indicate time passing,
and it is passing,
though where it’s going
nobody seems to know.
Something is always lost
and something found —
an earring or the key
to a certain door,
to some second self.
I watch as energy and matter
bow and switch places,
as last year’s leaves appear
and disappear again.”
(Linda Pastan, 1932- )
Rose in the Park
“Michelangelo: Divine Draftsman & Designer” (The Metropolitan Museum of Art, November 13, 2017 – February 12, 2018)
The Metropolitan Museum of Art recently had on view an internationally acclaimed exhibition, “Michelangelo: Divine Draftsman & Designer”, which closed on February 12th. Of the 600 drawings attributed to the great genius of the Italian Renaissance, the show brought together 133 of them from all over the world, the largest number of such works ever assembled by the Master. In addition, the show offered a handful of sculptures by Michelangelo as well as many rare preparatory “cartoons” and one of his early paintings. Drawings, paintings, and sculptures from the hands of other great artists of the period, including those in Michelangelo’s inner circle, were on hand, along with art from other eras serving to drive home essential ideas about what influenced him and why. One of the larger galleries boasted a brightly lit, small-scale reproduction of the Sistine Chapel’s famous ceiling, which hovered above the large space. Many of the drawings in that room were studies for specific images from the Chapel and each of the placards highlighted exactly where you could locate them above on the ceiling. These included a preliminary sketch of God’s reaching arm for the touch that will enliven Adam’s soul, the faces and bodies of the Sybils (including the well-known sheet in the Met’s collection, Studies for the Libyan Sibyl), and a letter written by Michelangelo with a tiny self-portrait illustrating the physical misery of this huge undertaking.
Just days after I had seen the exhibit, the curator, Dr. Carmen C. Bambach, and Research Assistant Jeffrey Fraiman who was deeply involved with many of the logistics of the project, invited me for an afterhours viewing with only about 25 others in attendance. I jumped at the opportunity.
Given this chance of a lifetime, for what end would I use it? One of the first major exhibitions I had ever attended, was in 1980 at the Morgan Library, “Michelangelo and His World”, which brought together 41 of the Master’s drawings. I specifically recall my strategy on studying his drawings at that visit, and this time, I specifically chose to take the exact opposite approach to understand the profound ideas revealed by the drawings. One can demand that the works of art assist with the progression of one’s own personal theories in hope of completing aesthetic, spiritual, or mystical inner dimensions within the soul or psyche. Upon entry to the Michelangelo exhibition, I said to myself: “Rubbish to all that,” and dove in simply to look at the drawings in the hope of experiencing what Kenneth Clark’s aptly calls “Moments of Vision”.
The Michelangelo exhibition gave its audience a chance to discover hints of how a genius of the highest level worked out his ideas. Viewers can see first-hand how his creative process initiated, perhaps as a work on paper in charcoal or in the wonderful textures induced by red chalk, and ended up as the sublime perfection of the frescoes in the Vatican or the perfect sculptures of The David or The Moses. The long-dead Michelangelo can’t go on camera and reveal how he did it so we are left in the uncomfortable situation of having to imply what his thinking process may have been by examining the clues he left behind and mixing them with tales of his personality gleaned from the reports at the time about his life or writings of his friends, such as Girogio Vasari in “The Lives of the Artists”.
The Met’s staff, including Dr. Bambach and Mr. Fraiman, do the tireless groundwork for all of us prior to our visit. They comb through the complicated historical record and centuries of scholarship, subsequently devising and writing up their theories. Dr. Bambach and Mr. Fraiman and their colleagues perform the Herculean task of condensing centuries of study and ideas so that their impressively educated passion sparks the hearts and minds of each one of the more than 600,000 people who viewed show.
A sheet of paper in one of the first galleries held numerous drawn studies of varying images by Michelangelo, some popping into the viewer’s eyes seemingly out of nowhere and retreating as another one emerged in its place. The drawing was crammed tight with idea after idea. On one side, I found of great interest an incomplete profile of a man buried in all the images of faces and bodies, fabulous in solid, confident detail, yet unusually halted in its progression. Other drawings in nearby galleries had isolated sketches on the same page floating in their own spatial realms and aesthetic dimensions, worked out by strokes of chalk, charcoal or pen. Many drawings were fully formed, or at times, there would be a section of a lightly present image next to another in sharp detail, reminiscent of da Vinci’s obsessive sketches in his famous notebooks.
Two of the rare works in the exhibition were large planning “cartoons”, one a section of a preparatory drawing for Michelangelo’s Vatican frescoes, depicting a detail of Roman soldiers for The Crucifixion of Saint Peter in the Pauline Chapel. The second was a design attributed to the Master and his workshop for Michele di Jacopo Cosini’s painting, Venus Kissing Cupid (the finished painting was also on view). The Vatican fragment left me engulfed in pure amazement and overwhelming awe. The Pauline paintings in the Vatican are of a completely different nature than the Sistine Chapel’s ceiling and Last Judgement wall. They seem to present an intense inner contemplative expression of Michelangelo’s suffering and spiritual conflicts. The frescoes have a tightness and harsher spatial reality of personal tortured reality than the grand images in the Sistine. Yet the cartoon at the Met had aspects of softness and clarity not apparent in the completed project.
Other highlights of the exhibition included a powerful sculpted bust depicting Brutus, displayed alongside an ancient Roman sculpture of a similarly posed emperor. There was also a sublime unfinished sculpture ambiguously titled, Apollo-David, similar in its chiseled texture to the unfinished Deposition in Florence in which a self-portrait of Michelangelo appears as Nicodemus. These sculptures are fabulously rough as opposed to the polish of Pietà in Saint Peters in Rome.
A room with red chalk drawings of unparalleled genius had depictions of emotional subjects such as Study for a Descent from the Cross and the dynamic display of Archers Shooting at a Herm. I found myself incapable of thinking about anything besides their exceptional power and beauty. I also found myself returning a number of times to gaze at the Unfinished Cartoon of the Virgin and Child. The face of the Madonna is similar in its features to many of the faces in the frescoed Sistine Chapel. The delicacy of the figure is ethereal, almost beyond physical reality, and well past thoughts of flesh and blood, perhaps created in the Master’s mind from his vision of the Platonic form of feminine beauty itself. His ideal became the blueprint for artists of the time in representing the divine in the guise of paint.
Michelangelo was a captive of the times in which he lived, as we all are. He had to create within the confines of the ideas, society, culture, and territorial realities of Italy during his lifespan of 1475-1564. Michelangelo guided art into a new paradigm reaching untold heights and revealing realms of ideas and thoughts on all manners of subjects, both human and spiritual in nature. We can all thank him for his efforts as well as those who continue to study the works of all of the greats and present them to us for the betterment of Mankind.
Michelangelo Buonarroti Roman Soldiers, Cartoon Fragment for the Lower Left Part of the Crucifixion of Saint Peter in the Pauline Chapel. Charcoal, with some black chalk, on approximately nineteen sheets of paper, outlines pricked for transfer. Museo Nazionale di Capodimonte, Gabinetto Disegni e Stampe, Naples (and detail).
Michelangelo Buonarroti Sketches of the Virgin, the Christ Child Reclining on a Cushion, and Other Sketches of Infants. Pen and brown ink. Staatliche Museen zu Berlin, Kupferstichkabinett.
LEFT: Mural Fragment of a Male Nude in Three-Quarter Length (Triton or Satyr). Charcoal on rough porous plaster. Sernesi Family, Villa Michelangiolo, Settignano;
CENTER: Bastiano (Aristotile) da Sangallo (Italian, 1481–1551). Copy after the Central Episode of the Bathers in Michelangelo’s Battle of Cascina.
Michelangelo Buonarroti (with slight retouching by a later hand in pen and ink). Unfinished Cartoon of the Virgin and Child. Black chalk, red chalk, traces of brush and brown wash, with lead-white gouache highlights. Casa Buonarroti, Florence.
Michelangelo Buonarroti with some assistance by Tiberio Calcagni Bust of Brutus (unfinished). Carrara marble. Museo Nazionale del Bargello, Florence.
View of the two galleries of the Met Museum’s exhibition “Michelangelo: Divine Draftsman & Designer”.
Vanessa J. Wu
Flip Sigi has been a long time coming. This Filipino taqueria is headed by Chef Jordan Andino who was born in Canada, grew up in California. He takes inspiration from his Filipino grandmother and draws on skills from the time he spent working in fine dining.
Jordan’s first restaurant in the West Village was originally named 2nd City, but has now joined the second restaurant located on the Upper East Side (UES) in sharing the name Flip Sigi.
With two locations, limited edition menu specials every month, and collaborations with other businesses, there’s always something new to experience, but always with a hint of familiarity, maybe even nostalgia. And don’t forget the distinctive hot sauces! There’s 1st Base, 2nd Base, 3rd Base, and Jordan’s very own recipe: Home Run. Put it on your burritos, bowls, burgers, and even Bloody Marys for an extra kick!
Like his hot sauce, Jordan is anything but bland. I had the pleasure of meeting him, and his energy is always so high that you’ll probably feel it leaping off the page!
NS: What is the meaning behind the name Flip Sigi?
JA: Flip Sigi basically means “Go Filipino” coming from a play on the words ‘Flip’ – Filipino and ‘Sigi’ – which basically means go!
NS: Why do you think Filipino food is gaining momentum?
JA: Filipino food is gaining momentum because, as a whole cuisine, it speaks to the 3 major cuisines that are popular and understood in the United States: Chinese, Spanish, and American. The fact that Filipino food has all these small elements people are familiar with will make them more keen to try something new.
NS: I know you take inspiration from your grandmother’s Filipino recipes. Why do you choose to remake other known foods with a Filipino take rather than traditional Filipino dishes?
JA: I like to remake the classic dishes because it helps introduce my culture and cuisine to a wider range of palates. The more that try it, the more people get introduced to my culture via my cuisine.
NS: What are your hopes for the future of your restaurants? Any specific goals?
JA: I hope my future restaurants will be great in number and widely respected among my cohorts and peers. Ideally, we create a culture, company, and restaurant that all people from the US can feel comfortable going to and eating at!
NS: How has your Californian identity influenced your food? As a Californian myself, I actually do get quite a bit of a Californian vibe from your food, your personality, and, to some extent, your restaurant decor!
JA: I would say that California influences my restaurants in two different ways: in my use of avocado and my vibe! I can’t help but love that laid-back feeling while trying to eat because it’s just how I was raised!
NS: Why did you choose New York to open your restaurants in?
JA: I opened in NYC because as cliché as it sounds, when it comes to food, if you can prove yourself successful here, you’re now universally respected.
NS: Why the UES and West Village neighborhoods specifically?
JA: Luckily for me, both the West Village and UES locations came from great contacts in the real estate business. We initially searched [in the West Village] because the reputation that restaurants have in this neighborhood is that of class and quality. We just had to be here to establish our brand as food-serious. We initially searched [on the UES] because with the opening of the 2nd Avenue Q train, this area will eventually be a hotbed of youth and an area that will attract guests in our price range.
NS: Is there anything that sets apart your UES location and your West Village location other than what’s explicitly on the menu and what’s on the “secret menu?”
JA: The locations are the same but have different fingerprints, so to speak. We want each place to have their own identity for the neighborhood that they’re part of.
NS: Of all your monthly specials and collabs thus far, which would you say is your personal favorite? I was a fan of the December longanisa poutine. You should definitely make that a regular item!
JA: I’ve done so many of the specials and collabs that it’s hard to remember. I’d say my two favorites are the Flip N Out Burger and the Sinigang Flip Bowl. Both are regular menu items now, but started as specials! Although I do agree: the longanisa poutine was insane!
NS: What about your favorite non-rotating menu item?
JA: Favorite non-rotating menu item – Cali Burrito.
NS: I saw that you’re going to be a part of the Food Show at the Javits Center in March. What are you planning on demo-ing? Anything from Flip Sigi?
JA: For the food show in March, I’m going to be on center stage demo-ing the highlights of Flip Sigi as well as some fun hacks for the general cook.
NS: Bonus Question: In-N-Out or Shake Shack?
JA: In-N-Out for life!!!!
The author with Flip Sigi’s chef, Jordan Andino.
From left to right 1) Flip Bowl: one of Jordan’s favorite limited-edition item, now here to stay; 2) Longanisa Poutine: Natural Selection’s Vanessa’s favorite limited-edition item; 3) Cali Burrito: Jordan’s favorite regular menu item.
Flip Ramen: The first limited edition item of 2018 – a ramen with both chicken and pork adobo!
L.A.E. Me: a collab with black seed bagels now on the official Flip Sigi menu – longanisa, American cheese, and a fried egg on an everything bagel.
Poke Me: a twist on the classic tuna poke bowl served with sweet miso coconut steamed rice.
For my review of this restaurant and others: vanessajwu.yelp.com
For more photos from this restaurant and others: instagram.com/vanessajwu
I’m confused, disoriented. The ringing from my alarm still in my ear, I’m performing the absolute minimum necessary number of tasks that prepare me to go out and join the herd of zombies slowly moving through the streets. Phasing in and out of consciousness, me and my fellow undead finally manage to stumble into the same type of place, as if we had all been drawn there by an invisible force. It is here, where I get what I crave: A black magic juice whose ingestion will allow me to start feeling like a human being for the first time that day. What I crave, of course, is coffee.
I might be slightly exaggerating for dramatic effect, which doesn’t make it less true that many people all around the globe rely on a good morning cup of joe as an essential part of their daily routine. But recently, those people started to grow increasingly worried as news outlets have begun reporting that the State of California wants to force coffee shops and other places that sell brewed coffee to label it as cancerogenic. So clearly, many are now asking: Have we been drinking poison the whole time?
Let’s back up a moment: Since 1986, California law requires all companies with 10 or more employees to post clear warnings on or around products that could pose a danger to a potential consumer (apparently, if your company has only 9 employees you’re allowed to give people cancer, but let’s not go there). This risk is defined by a product containing certain chemicals that are listed in the law’s documentation, among them, one at the center of this debate: acrylamide. Acrylamide is formed as a byproduct of the Maillard reaction, which occurs pretty much anytime food items (especially starchy ones) are heated over a certain temperature. This reaction is responsible for the crust on a seared steak, the dark rind of a freshly baked loaf of bread, or the crispy exterior of a french fry (you know, all the good stuff). And—you guessed it—coffee beans owe their beautiful brown sheen to this chemical reaction happening during the roasting process.
So how dangerous is acrylamide? Well, it all depends on how you look at it. The results of studies in which mice and rats had been fed with the chemicals have shown a clear dose-dependent correlation between cancer and acrylamide. Taking these results at face value, we could fairly confidently assume that acrylamide will have a cancerogenic effect on humans as long as—and this is important—one ingests enough of it. I’m stressing this fact, because the amount of acrylamide the rodents were exposed to in these laboratory experiments are 1,000 – 100,000 times higher on a per kilogram basis than what can be expected from dietary consumption in humans, which makes it very unlikely that one can take up enough dietary acrylamide to cause immediate harm.
Of course, this fact doesn’t exonerate acrylamide just yet. What about long-term exposure of humans to small amounts of this compound? This is where it gets complicated. You see, long-term dietary studies are usually quite tricky to perform, control, and analyze well. This is due to many reasons, with one of the most problematic being the reliance of many studies on their subject’s self-reporting and our tendency to (willingly or unwillingly) misrepresent the number of things we put into our mouths. Nonetheless, these studies have been scientists’ bread and butter (no pun intended) for decades, allowing them to assess the influence of diet on our health. And up to this day all of these studies have failed to prove a clear correlation between acrylamide in cancer in humans. This means that from all the information we have so far, we can assume that it is unlikely that the concentrations found in a normal human diet (including in coffee) will have any measurable effect on your health. In particular, your cancer risk is way more likely to be influenced by factors such as genetics, certain habits, such as smoking, or whether you are occupationally exposed to higher concentrations of chemicals or radiation. But, as I mentioned, our current studies aren’t perfect, which is why the National Cancer Institute suggests additional epidemiological long-term studies that do a better job tracking certain metabolic markers.
But now let’s get back to coffee. Should you stop drinking it because of acrylamide? Probably not. Should it get a label because of its acrylamide content? Probably not. Even so, you might say to yourself: “Well, let’s just play it safe and cut the coffee”. In this case; however, I want you to consider this: In 2014, the results of a meta-analysis of 21 studies conducted between 1966 and 2013 showed that coffee consumption of 3-4 cups per day was not only not correlated with cancer mortality, but even decreased (!) the likelihood of death from all causes and also specifically from cardiovascular disease. So, the next time you want to reach for this expensive face cream behind your bathroom mirror, think about going into your kitchen instead, because those little brown beans on the counter might hold the actual secret formula for longevity. Black magic juice, indeed.
“When all the trees have been cut down, when all the animals have been hunted, when all the waters are polluted, when all the air is unsafe to breathe, only then will you discover you cannot eat money.”
Winter’s gone, or has it? Even if most of the cold months are behind us, it might be too early to take out our spring trench coats. On February 2, Groundhog Day was celebrated across the United States, but this year’s forecast was dire. Contrasting predictions between Pennsylvania’s famous Punxsutawney Phil and Staten Island’s very own Chuck left the case unsettled, so we might still have a few weeks of biting weather ahead of us. To play it safe, let’s look at some indoor entertainment options:
- Bake. This is your chance to ask your cute neighbor for a cup of sugar! There are billions of recipes online, which sometimes require an overwhelming amount of kitchen gear. Whether you’re a beginner or a seasoned baker, muffins are always a good idea. They’re just as delicious as they are simple to prepare, and once you master the “muffin technique” (see blogs like myrecipe.com or kitchn.com for easy recipes) you’ll be able to wow your loved ones with elaborate flavor combos. Think apple-cheddar or dark chocolate-bacon muffins. Next thing you know, you’ll learn how to frost and fight on “Cupcake Wars”. Pros: baking will make your apartment cozy and smell delicious. Cons: some clean up required.
- Join a wine club. Wine clubs are a good opportunity for many reasons. You like to experiment with different wines but don’t have much time to browse in local shops? Wine club. You dread inevitable conversations with the too well-meaning salesperson and want to get a good price on bottles? Wine club. Get a feeling for which subscription could work for you on websites like net. Also, you’ll have plenty of reasons to enjoy another fun indoor activity: throwing wine tasting parties. Pros: show off the cheese knife set you bought yourself at Pottery Barn a year ago. Cons: now your friends will know better if you show up with “2 bucks-a-bottle-with-pretentious-label” wine.
- Play board games. A great reason to put down our phones and computers, and actually socialize. If you’re asking yourself why you should try it, consider the many benefits associated with playing board games. Besides enhancing brain function, board games are known to help reduce stress, increase creativity and strengthen relationships. If the last board game you played was either Scrabble or Monopoly, then you’re in for a big surprise. Adult board game options are now countless. Just to name a few: Settlers of Catan, Cards Against Humanity, Exploding Kittens, and What Do You Meme? With updated options like these, you’re bound to have fun. If you’re looking for someone to play with, you should know that New York City is home to The Uncommons, a board game café with one of the largest library of games on the East Coast. Pros: the perfect occasion to spend time with friends and family while wrapped in a sleeved blanket. Cons: too much fun?
- Knit. Yes, I’m serious. I’ll argue that knitting is one of the very few mindfulness activities that actually results in something useful. You can choose to actively pay attention to every stich, or, much like doodling, simply keep your hands busy while your mind focuses on other things. Crafts can be very rewarding, crushingly cute (ex. baby hats. Enough said), and of all shapes and sizes. If you’re already comfortable with needles and infinity scarfs, challenge yourself with quirkier artwork, such as knitted cactus vases or faux taxidermy. Pros: you won’t ever have to worry about buying gifts again. Cons: the inevitable learning curve and your supplies may be bulky to carry around.
As much as we all hope Staten Island Chuck was right, winter time gives us a chance to get creative indoors. At the very least, we should be prepared in case a snow storm cuts out the WIFI.
noun | wom·an | ˈwu̇-mən , especially Southern ˈwō- or ˈwə- |
an adult female person
The word’s primary definition is simple enough: according to Merriam-Webster, a woman is “an adult female person.” Also according to Merriam-Webster, it is in the top 10% of most-used online words. This is hardly a surprise. Feminism (a noun which Merriam-Webster defines as “the advocacy of women’s rights on the basis of the equality of the sexes”) is now in its fourth wave. Its current focus is on using social media to amplify opposition to all-too-common phenomena of violence against women, with an emphasis on sexual harassment. Feminism is seeping into popular culture as well. Beyonce’s song ***Flawless, for example, samples Chimamanda Ngozi Adichie: in the middle of the song, we hear the activist read a few lines from her now-famous speech “Why We Should All Be Feminists.” Adichie says, “We teach girls to shrink themselves, to make themselves smaller. We say to girls: You can have ambition, but not too much. You should aim to be successful, but not too successful. Otherwise, you will threaten the man.”
This brief excerpt highlights what is most interesting to me about woman’s definition: in these few lines, Adichie reinforces the word’s inherent binary. Through the comparison of women to men (specifically, of girls to boys), she places women on one side of this binary, and men on the other. Interestingly, this binary is also reflected in the language: while a woman is defined as a “female person,” a man, according to Merriam-Webster, is “an individual human; especially an adult male human.” The gendered caveat of the word man lies only in the qualifying clause, skewing baseline humanity with maleness. Woman’s etymology further supports this: it is derived from the Old English word wifman, which itself combines the words wife and man—the former being the Old English synonym for woman, the latter being synonymous for human. The word “man” not only has more definitions than woman, but these definitions also extend beyond the confines of gender and even traverse into different parts of speech (the verb meaning to control or supply, for example). So not only is the word woman binarized, it is also linguistically upholds a gendered inequality. However, this binary does not solely exist within the confines of the language; it has somewhat insidiously entrenched itself into the norms of our culture. In fact, it is so subtly embedded that it can impact the way in which women think and feel about themselves and each other.
The word is especially appropriate given that March is Women’s History Month. It has been recognized as such in the United States only since 1995; before this, starting in 1981, just one week in March was celebrated as Women’s History Week. This week, and later the month, builds on the celebration of International Women’s Day on March 8th, which has been recognized in the United States since the year 1909, but was only recognized by the United Nations starting in 1975. (It became a national holiday in Soviet Russia in 1917.) The resilience of the women’s movement is always striking when its history is considered, particularly in a country like the United States, which touts equality and progressivism in its ideological foundations. Women’s History Month has only, within the past twenty-odd years, been adopted as a mainstream, national holiday. It can be disheartening to think about how much more work needs to be done, particularly when the definition of the word “woman” upholds an innate inequality. Yet, one of language’s most beautiful characteristics is that it can be fluid and dynamic; with work, the norms embedded both in our language and our society have the potential to change.
Editor’s note: This article was originally published as Twenty-four visits to Stockholm: a concise history of the Rockefeller Nobel Prizes by Joseph Luna in June 2016.
Günter Blobel (May 21, 1936 – February 18, 2018)
Let’s start with a fantastical scene: picture a band of Neolithic humans in a hot air balloon overlooking modern New York City. What would they see and experience? Lacking a vocabulary and a mental model of twenty-first century life, our ancient friends would be awestruck at seeing miniscule specks and strangely ordered structures, lines and squares, in green and gray. Perhaps the occasional yellow rectangle from which specks would enter and exit would catch their attention. Or they might ponder a box with flashing lights, speeding its way across a grid. It’s near impossible to imagine being in their shoes, but it’s easy to envision the excitement as they try to describe and make sense of what they saw.
This totally novel experience wasn’t far off from what early cell biologists encountered, as they used the electron microscope (EM) as a sort of hot-air balloon to discover the cities inside cells. By the mid-1960s, they had plotted the geography of all sorts of cellular worlds, had given names to energy-making blobs and recycling vesicles, and with the help of radioactive amino acid labeling, had a basic sense of where proteins were made and where they ended up. But big questions remained such as how did a protein know where it needed to go? For a discipline built on EM observations from high above, this was a challenging question to answer, but it captivated a young German post-doc enough to dream as if he landed his hot air balloon and walked among molecules, where the view was much clearer.
Günter Blobel arrived in George Palade’s laboratory in 1967, shortly after completing his PhD at the University of Wisconsin at Madison. He joined a dynamic group of researchers who had stumbled upon an odd observation concerning the protein factories of the cell, its ribosomes: proteins destined to remain inside the cell were often made from a pool of freely cytoplasmic ribosomes, whereas proteins meant to be exported from the cell quickly associated with ribosomes attached to the endoplasmic reticulum (ER). How a new protein made this decision to stay in the cytoplasm or go to the ER was a mystery.
Within a few years, and overwhelmingly without much evidence, Blobel and a colleague (and Rockefeller University alum) named David Sabatini formulated what became known as “the signal hypothesis” that might explain how proteins got sorted to their proper locations. It represented a truly imaginative and startlingly precise leap, as if one could envision a five digit postal code and a stamp authentication system simply by watching mail trucks from space. Blobel and Sabatini proposed that ER destined proteins contained a special stretch of amino acids that acted like a signal that became apparent the moment the protein was being made at a ribosome. This signal sequence, located at the head of a protein, would be recognized by a factor (or factors) that would, in turn guide the synthesizing ribosome to the ER, where the protein in question could finish being born as it translocated across the ER membrane. Once properly sorted into the ER, the signal sequence was no longer needed and could be removed by an enzyme, even while the protein was still being made. Once finished, the protein could then go and do its job.
For many, this all sounded needlessly baroque. One attractive alternative was to consider different types of ribosomes, where each type was responsible for ferrying a nascent protein to a particular location. Another idea postulated that the mRNAs encoding proteins somehow got to the correct place before undergoing translation from any nearby ribosome. The signal hypothesis was one of many possible models, and a far-fetched one at that. But it made very precise predictions that could be tested, the first of which was the existence of a transient signal sequence.
Myeloma cells provided the first toe-hold for testing the signal hypotheses, since they secreted lots of IgG antibody light chains that could be readily detected. Using cell-free translation systems, based on these cells, other laboratories had observed slightly heftier IgG molecules than those secreted from intact cells, suggesting that a larger precursor was made and pruned to a final, smaller form. Yet, worries of an in vitro artifact abound. Blobel first repeated this experiment, and once confirmed, tinkered with his cell free system to uncover the order of events. Using detergent, he separated ribosomes from bits of ER (called microsomes) and added a drug that blocked new IgG production. He then let the ribosomes that had already started making an IgG to finish, keeping track of what they produced and when. Early in the experiment, only the smaller form emerged, which made sense if these ribosomes had already been at the ER and were nearly finished making IgG when Blobel had isolated them. But later in the experiment, a mixture of larger and smaller forms showed up: ribosomes that had just started making IgG indeed made a larger version. But lacking sufficient ER targeting, the signal sequence wasn’t pruned efficiently. Blobel had glimpsed a totally new feature in the early lives of proteins.
This was just the start. Over the ensuing years, Blobel and his team devised ways of recapitulating numerous aspects of protein targeting in the cell, from isolating the complex that ferried a signal sequence bearing protein to the ER (the aptly named “signal recognition particle”) to later confirming and characterizing the protein channel at the ER (the translocon) that nascent proteins traversed for proper processing. In part because of Blobel’s efforts, the hot air balloon view gave way to detailed explorations from the ground. A dream, as all good hypotheses are, turned out to be true.
This month Natural Selections interviews Robert Gualtieri, Plant Operations
How long have you been living in the New York area?
Practically all my life, I was born and raised in Upper West Harlem, with the exception of 4 to 5 years that I lived in Puerto Rico.
Where do you currently live? Which is your favorite neighborhood?
The Heights, in Washington Heights. I don’t feel like I have a favorite neighborhood, for me it’s more like spending good times in certain areas of the city that become favorite memories.
What do you think is the most overrated thing in the city? And underrated?
The most overrated thing in the city are the new buildings with rents that are not affordable, and the most underrated are the people that can’t afford high rents.
What do you miss most when you are out of town?
I would say everything…the lights, the sound escapes, the 24-hour grocery stores, just everything the city offers.
Has anything (negative or positive) changed about you since you became one of us “New Yorkers”?
Well, I’m a native New Yorker. So, I’m trying to keep a positive disposition with everything that’s rapidly changing and taking place here in the City.
If you could change one thing about NYC, what would that be?
I feel I’ll pass on this question, lol.
What is your favorite weekend activity in NYC?
Staying up late listening to music (vinyl or live is even better), I dedicate myself to the arts; so, weekends allow me to concentrate on creating new works or sharing time with some of my friends that are in the arts musically or visually.
What is the most memorable experience you have had in NYC?
I have to say writing my name on the subway trains in 1970 when I was 14, and watching my name go by as I sat on the bench at the station with other writers.
Bike, MTA, or WALK IT???
It all depends where I have to go; sometimes I drive, take mass transit, or cab it.
If you could live anywhere else, where [would] might that be?
I’ve been to a number of cities worldwide, and entertained the thought that I can live there during my stay. After a couple of weeks, I get homesick and want to return to NY, so for now I’ll just say that I’m not sure.
Do you think of yourself as a New Yorker?
If I don’t think I do by now, I don’t think I ever will.
In the Middle of Paris France
The Saint-Jacques Tower, with its flamboyant gothic style, is located in the middle of Paris. It is all that remains of a church built in the 16th century and demolished during the French Revolution. The 171-foot tower has had many functions since then (including a shot tower!) and undergone many phases of restoration. It is now open to the public (tour guide only), and the view from there is simply stunning.