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.
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 smit·ten \ ˈsmi-tᵊn \
deeply affected with or struck by strong feelings of attraction, affection, or infatuation
The month of February often conjures up the all too familiar images related to Valentine’s Day: heart-shaped chocolates and balloons, bouquets of flowers, and Hallmark cards passed between young children at school and between romantic partners. In the United States, Valentine’s Day is a day dedicated to celebrating love—often, to celebrate the state of being smitten.
I am interested in this particular word because, in addition to its form as an adjective, smitten is also the past participle of smite. Smite, a verb, has two definitions, the first of which is “to be strongly attracted to somebody or something,” or “to captivate.” In the context of this definition, the derivation of the adjective smitten is intuitive. However, smite’s second definition takes a dramatic 180° turn, from something soft to something harsh and violent: “to take,” or “to strike with a firm blow.”
According to Merriam-Webster, smite originates from a twelfth century Middle English word meaning to smear or defile; the dictionary likens it to an Old High German word with a similar meaning. As it relates to romantic love, this definition is almost paradoxical. Perhaps “captivate” or “take” make sense (Merriam-Webster’s example sentence cites being captivated by a woman’s beauty), but for this word to also be defined by violence produces a fascinating contradiction: why are the two linked?
To answer this question, we can look to another common Valentine’s Day symbol that stems from Greek and Roman mythology: the God of love, Cupid. Usually portrayed as a young and winged boy, Cupid is armed with a bow and arrow; anyone who is struck by one of his arrows, mortal or not, is overcome by affection and love. Cupid’s very existence takes into account both sides of smite’s definitions: the first being the gentle inspiration of love; the second being the violent mechanism by which love is inspired. In some depictions, he is wearing armor as he works to matchmake. This begs the question: does this interpretation fall into the softer definition of smite, suggesting that love is invincible or impenetrable? Or does it fall into the harsher one, likening love to war?
Perhaps these definitions cannot be parsed into a binary. Instead, perhaps they must be considered together, particularly in the context of romance, of love, and of relationships generally. In the past six months in the United States, there has been a massive eruption of reports of sexual misconduct, particularly regarding high-profile and powerful men. The catalyst was Ronan Farrow’s exposé on Harvey Weinstein in the New Yorker, and from it has stemmed a resurgence of activist Tarana Burke’s social media hashtag #MeToo. Now known as the MeToo movement, the premise is, according to Burke, to “promote empowerment through empathy” by sharing among women, particularly those who are vulnerable (for example, young women of color), the all too prevalent experience of sexual misconduct. Alyssa Milano, an actress who encouraged spreading the hashtag after the stories of Weinstein surfaced, explained it as follows: “If all the women who have been sexually harassed or assaulted wrote ‘Me too.’ as a status, we might give people a sense of the magnitude of the problem.”
It is important to dissociate from love the type of behavior displayed by Weinstein (and many, many others). However, it is equally important to remember the duality of smite’s definition, and to remember Cupid’s bow and arrow, and armor when thinking about love and relationships as they exist today, particularly in the context of the MeToo movement. Those in positions of power have been forced to confront the issue of accountability, some for the first time, and these considerations will then hopefully trickle down into more of an awareness when it comes to fair and healthy relationships.
When one is smitten, one is, according to the word’s definition, “deeply affected” by feelings. It is imperative to take into account the depth of this impact. As the language suggests, relationships—and love—hold great power.