The award-winning New York Times science writer Carl Zimmer.
(Courtesy of Zimmer)
Carl Zimmer, the award-winning New York Times science writer, recently published a stellar book about human heredity called "She Has Her Mother's Laugh." Truly a magnum opus, the book delves into the cultural and scientific evolution of genetics, the field's outsize impact on society, and the new ways we might fundamentally alter our species and our planet.
"I was only prepared to write about how someday we would cross this line, and actually, we've already crossed it."
Zimmer spoke last week with editor-in-chief Kira Peikoff about the international race to edit the genes of human embryos, the biggest danger he sees for society (hint: it's not super geniuses created by CRISPR), and some outlandish possibilities for how we might reproduce in the future. This interview has been edited and condensed for clarity.
I was struck by the number of surprises you uncovered while researching human heredity, like how fetal cells can endure for a lifetime in a mother's body and brain. What was one of the biggest surprises for you?
Something that really jumped out for me was for the section on genetically modifying people. It does seem incredibly hypothetical. But then I started looking into mitochondrial replacement therapy, so-called "three parent babies." I was really surprised to discover that almost by accident, a number of genetically modified people were created this way [in the late 90s and early 2000s]. They walk among us, and they're actually fine as far as anyone can tell. I was only prepared to write about how someday we would cross this line, and actually, we've already crossed it.
And now we have the current arms race between the U.S. and China to edit diseases out of human embryos, with China being much more willing and the U.S. more reluctant. Do you think it's more important to get ahead or to proceed as ethically as possible?
I would prefer a middle road. I think that rushing into tinkering with the features of human heredity could be a disastrous mistake for a lot of reasons. On the other hand, if we completely retreat from it out of some vague fear, I think that we won't take advantage of the actual benefits that this technology might have that are totally ethically sound.
I think the United Kingdom is actually showing how you can go the middle route with mitochondrial replacement therapy. The United States has just said nope, you can't do it at all, and you have Congressmen talking about how it's just playing God or Frankenstein. And then there are countries like Mexico or the Ukraine where people are doing mitochondrial replacement therapy because there are no regulations at all. It's a wild west situation, and that's not a good idea either.
But in the UK, they said alright, well let's talk about this, let's have a debate in Parliament, and they did, and then the government came up with a well thought-through policy. They decided that they were going to allow for this, but only in places that applied for a license, and would be monitored, and would keep track of the procedure and the health of these children and actually have real data going forward. I would imagine that they're going to very soon have their first patients.
As you mentioned, one researcher recently traveled to Mexico from New York to carry out the so-called "three-parent baby" procedure in order to escape the FDA's rules. What's your take on scientists having to leave their own jurisdictions to advance their research programs under less scrutiny?
I think it's a problem when people who have a real medical need have to leave their own country to get truly effective treatment for it. On the other hand, we're seeing lots of people going abroad to countries that don't monitor all the claims that clinics are making about their treatments. So you have stem cell clinics in all sorts of places that are making all sorts of ridiculous promises. They're not delivering those results, and in some cases, they're doing harm.
"Advances in stem cell biology and reproductive biology are a much bigger challenge to our conventional ideas about heredity than CRISPR is."
It's a tricky tension for sure. Speaking of gene editing humans, you mention in the book that one of the CRISPR pioneers, Jennifer Doudna, now has recurring nightmares about Hitler. Do you think that her fears about eugenics being revived with gene editing are justified?
The word "eugenics" has a long history and it's meant different things to different people. So we have to do a better job of talking about it in the future if we really want to talk about the risks and the promises of technology like CRISPR. Eugenics in its most toxic form was an ideology that let governments, including the United States, sterilize their own citizens by the tens of thousands. Then Nazi Germany also used eugenics as a justification to exterminate many more people.
Nobody's talking about that with CRISPR. Now, are people concerned that we are going to wipe out lots of human genetic diversity with it? That would be a bad thing, but I'm skeptical that would actually ever happen. You would have to have some sort of science fiction one-world government that required every new child to be born with IVF. It's not something that keeps me up at night. Honestly, I think we have much bigger problems to worry about.
What is the biggest danger relating to genetics that we should be aware of?
Part of what made eugenics such a toxic ideology was that it was used as a justification for indifference. In other words, if there are problems in society, like a large swath of people who are living in poverty, well, there's nothing you can do about it because it must be due to genetics.
If you look at genetics as being the sole place where you can solve humanity's problems, then you're going to say well, there's no point in trying to clean up the environment or trying to improve human welfare.
A major theme in your book is that we should not narrow our focus on genes as the only type of heredity. We also may inherit some epigenetic marks, some of our mother's microbiome and mitochondria, and importantly, our culture and our environment. Why does an expanded view of heredity matter?
We should think about the world that our children are going to inherit, and their children, and their children. They're going to inherit our genes, but they're also going to inherit this planet and we're doing things that are going to have an incredibly long-lasting impact on it. I think global warming is one of the biggest. When you put carbon dioxide into the air, it stays there for a very, very long time. If we stopped emitting carbon dioxide now, the Earth would stay warm for many centuries. We should think about tinkering with the future of genetic heredity, but I think we should also be doing that with our environmental heredity and our cultural heredity.
At the end of the book, you discuss some very bizarre possibilities for inheritance that could be made possible through induced pluripotent stem cell technology and IVF -- like four-parent babies, men producing eggs, and children with 8-celled embryos as their parents. If this is where reproductive medicine is headed, how can ethics keep up?
I'm not sure actually. I think that these advances in stem cell biology and reproductive biology are a much bigger challenge to our conventional ideas about heredity than CRISPR is. With CRISPR, you might be tweaking a gene here and there, but they're still genes in an embryo which then becomes a person, who would then have children -- the process our species has been familiar with for a long time.
"We have to recognize that we need a new language that fits with the science of heredity in the 21st century."
We all assume that there's no way to find a fundamentally different way of passing down genes, but it turns out that it's not really that hard to turn a skin cell from a cheek scraping into an egg or sperm. There are some challenges that still have to be worked out to make this something that could be carried out a lot in labs, but I don't see any huge barriers to it. Ethics doesn't even have the language to discuss the possibilities. Like for example, one person producing both male and female sex cells, which are then fertilized to produce embryos so that you have a child who only has one parent. How do we even talk about that? I don't know. But that's coming up fast.
We haven't developed our language as quickly as the technology itself. So how do we move forward?
We have to recognize that we need a new language that fits with the science of heredity in the 21st century. I think one of the biggest problems we have as a society is that most of our understanding about these issues largely comes from what we learned in grade school and high school in biology class. A high school biology class, even now, gets up to Mendel and then stops. Gregor Mendel is a great place to start, but it's a really bad place to stop talking about heredity.
[Ed. Note: Zimmer's book can be purchased through your retailer of choice here.]
Katalin Karikó, pictured, and Drew Weissman won the Nobel Prize for advances in mRNA research that led to the first Covid vaccines.
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The work for which they garnered the illustrious award and its accompanying $1,000,000 cash windfall was completed about two decades ago, wrought through long hours in the lab over many arduous years. But humanity collectively benefited from its life-saving outcome three years ago, when both Moderna and Pfizer/BioNTech’s mRNA vaccines against COVID were found to be safe and highly effective at preventing severe disease. Billions of doses have since been given out to protect humans from the upstart viral scourge.
“I thought of going somewhere else, or doing something else,” said Katalin Karikó. “I also thought maybe I’m not good enough, not smart enough. I tried to imagine: Everything is here, and I just have to do better experiments.”
Unlocking the power of mRNA
Weissman and Karikó unlocked mRNA vaccines for the world back in the early 2000s when they made a key breakthrough. Messenger RNA molecules are essentially instructions for cells’ ribosomes to make specific proteins, so in the 1980s and 1990s, researchers started wondering if sneaking mRNA into the body could trigger cells to manufacture antibodies, enzymes, or growth agents for protecting against infection, treating disease, or repairing tissues. But there was a big problem: injecting this synthetic mRNA triggered a dangerous, inflammatory immune response resulting in the mRNA’s destruction.
While most other researchers chose not to tackle this perplexing problem to instead pursue more lucrative and publishable exploits, Karikó stuck with it. The choice sent her academic career into depressing doldrums. Nobody would fund her work, publications dried up, and after six years as an assistant professor at the University of Pennsylvania, Karikó got demoted. She was going backward.
“I thought of going somewhere else, or doing something else,” Karikó told Stat in 2020. “I also thought maybe I’m not good enough, not smart enough. I tried to imagine: Everything is here, and I just have to do better experiments.”
A tale of tenacity
Collaborating with Drew Weissman, a new professor at the University of Pennsylvania, in the late 1990s helped provide Karikó with the tenacity to continue. Weissman nurtured a goal of developing a vaccine against HIV-1, and saw mRNA as a potential way to do it.
“For the 20 years that we’ve worked together before anybody knew what RNA is, or cared, it was the two of us literally side by side at a bench working together,” Weissman said in an interview with Adam Smith of the Nobel Foundation.
In 2005, the duo made their 2023 Nobel Prize-winning breakthrough, detailing it in a relatively small journal, Immunity. (Their paper was rejected by larger journals, including Science and Nature.) They figured out that chemically modifying the nucleoside bases that make up mRNA allowed the molecule to slip past the body’s immune defenses. Karikó and Weissman followed up that finding by creating mRNA that’s more efficiently translated within cells, greatly boosting protein production. In 2020, scientists at Moderna and BioNTech (where Karikó worked from 2013 to 2022) rushed to craft vaccines against COVID, putting their methods to life-saving use.
The future of vaccines
Buoyed by the resounding success of mRNA vaccines, scientists are now hurriedly researching ways to use mRNA medicine against other infectious diseases, cancer, and genetic disorders. The now ubiquitous efforts stand in stark contrast to Karikó and Weissman’s previously unheralded struggles years ago as they doggedly worked to realize a shared dream that so many others shied away from. Katalin Karikó and Drew Weissman were brave enough to walk a scientific path that very well could have ended in a dead end, and for that, they absolutely deserve their 2023 Nobel Prize.
This article originally appeared on Big Think, home of the brightest minds and biggest ideas of all time.
With conventional fuel cells as their model, researchers learned to use similar chemical reactions to make a fuel from microbes in pee.
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Plus, urine contains water, phosphorus, potassium and nitrogen, the key ingredients plants need to grow and survive. Human urine could replace about 25 percent of current nitrogen and phosphorous fertilizers worldwide and could save water for gardens and crops. The average U.S. resident flushes a toilet bowl containing only pee and paper about six to seven times a day, which adds up to about 3,500 gallons of water down per year. Plus cows in the U.S. produce 231 gallons of the stuff each year.
Pee power
A conventional fuel cell uses chemical reactions to produce energy, as electrons move from one electrode to another to power a lightbulb or phone. Ioannis Ieropoulos, a professor and chair of Environmental Engineering at the University of Southampton in England, realized the same type of reaction could be used to make a fuel from microbes in pee.
Bacterial species like Shewanella oneidensis and Pseudomonas aeruginosa can consume carbon and other nutrients in urine and pop out electrons as a result of their digestion. In a microbial fuel cell, one electrode is covered in microbes, immersed in urine and kept away from oxygen. Another electrode is in contact with oxygen. When the microbes feed on nutrients, they produce the electrons that flow through the circuit from one electrod to another to combine with oxygen on the other side. As long as the microbes have fresh pee to chomp on, electrons keep flowing. And after the microbes are done with the pee, it can be used as fertilizer.
These microbes are easily found in wastewater treatment plants, ponds, lakes, rivers or soil. Keeping them alive is the easy part, says Ieropoulos. Once the cells start producing stable power, his group sequences the microbes and keeps using them.
Like many promising technologies, scaling these devices for mass consumption won’t be easy, says Kevin Orner, a civil engineering professor at West Virginia University. But it’s moving in the right direction. Ieropoulos’s device has shrunk from the size of about three packs of cards to a large glue stick. It looks and works much like a AAA battery and produce about the same power. By itself, the device can barely power a light bulb, but when stacked together, they can do much more—just like photovoltaic cells in solar panels. His lab has produced 1760 fuel cells stacked together, and with manufacturing support, there’s no theoretical ceiling, he says.
Although pure urine produces the most power, Ieropoulos’s devices also work with the mixed liquids of the wastewater treatment plants, so they can be retrofit into urban wastewater utilities.
This image shows how the pee-powered system works. Pee feeds bacteria in the stack of fuel cells (1), which give off electrons (2) stored in parallel cylindrical cells (3). These cells are connected to a voltage regulator (4), which smooths out the electrical signal to ensure consistent power to the LED strips lighting the toilet.
Courtesy Ioannis Ieropoulos
Key to the long-term success of any urine reclamation effort, says Orner, is avoiding what he calls “parachute engineering”—when well-meaning scientists solve a problem with novel tech and then abandon it. “The way around that is to have either the need come from the community or to have an organization in a community that is committed to seeing a project operate and maintained,” he says.
Success with urine reclamation also depends on the economy. “If energy prices are low, it may not make sense to recover energy,” says Orner. “But right now, fertilizer prices worldwide are generally pretty high, so it may make sense to recover fertilizer and nutrients.” There are obstacles, too, such as few incentives for builders to incorporate urine recycling into new construction. And any hiccups like leaks or waste seepage will cost builders money and reputation. Right now, Orner says, the risks are just too high.
Despite the challenges, Ieropoulos envisions a future in which urine is passed through microbial fuel cells at wastewater treatment plants, retrofitted septic tanks, and building basements, and is then delivered to businesses to use as agricultural fertilizers. Although pure urine produces the most power, Ieropoulos’s devices also work with the mixed liquids of the wastewater treatment plants, so they can be retrofitted into urban wastewater utilities where they can make electricity from the effluent. And unlike solar cells, which are a common target of theft in some areas, nobody wants to steal a bunch of pee.
When Ieropoulos’s team returned to wrap up their pilot project 18 months later, the school’s director begged them to leave the fuel cells in place—because they made a major difference in students’ lives. “We replaced it with a substantial photovoltaic panel,” says Ieropoulos, They couldn’t leave the units forever, he explained, because of intellectual property reasons—their funders worried about theft of both the technology and the idea. But the photovoltaic replacement could be stolen, too, leaving the girls in the dark.
The story repeated itself at another school, in Nairobi, Kenya, as well as in an informal settlement in Durban, South Africa. Each time, Ieropoulos vowed to return. Though the pandemic has delayed his promise, he is resolute about continuing his work—it is a moral and legal obligation. “We've made a commitment to ourselves and to the pupils,” he says. “That's why we need to go back.”
Urine as fertilizer
Modern day industrial systems perpetuate the broken cycle of nutrients. When plants grow, they use up nutrients the soil. We eat the plans and excrete some of the nutrients we pass them into rivers and oceans. As a result, farmers must keep fertilizing the fields while our waste keeps fertilizing the waterways, where the algae, overfertilized with nitrogen, phosphorous and other nutrients grows out of control, sucking up oxygen that other marine species need to live. Few global communities remain untouched by the related challenges this broken chain create: insufficient clean water, food, and energy, and too much human and animal waste.
The Rich Earth Institute in Vermont runs a community-wide urine nutrient recovery program, which collects urine from homes and businesses, transports it for processing, and then supplies it as fertilizer to local farms.
One solution to this broken cycle is reclaiming urine and returning it back to the land. The Rich Earth Institute in Vermont is one of several organizations around the world working to divert and save urine for agricultural use. “The urine produced by an adult in one day contains enough fertilizer to grow all the wheat in one loaf of bread,” states their website.
Notably, while urine is not entirely sterile, it tends to harbor fewer pathogens than feces. That’s largely because urine has less organic matter and therefore less food for pathogens to feed on, but also because the urinary tract and the bladder have built-in antimicrobial defenses that kill many germs. In fact, the Rich Earth Institute says it’s safe to put your own urine onto crops grown for home consumption. Nonetheless, you’ll want to dilute it first because pee usually has too much nitrogen and can cause “fertilizer burn” if applied straight without dilution. Other projects to turn urine into fertilizer are in progress in Niger, South Africa, Kenya, Ethiopia, Sweden, Switzerland, The Netherlands, Australia, and France.
Eleven years ago, the Institute started a program that collects urine from homes and businesses, transports it for processing, and then supplies it as fertilizer to local farms. By 2021, the program included 180 donors producing over 12,000 gallons of urine each year. This urine is helping to fertilize hay fields at four partnering farms. Orner, the West Virginia professor, sees it as a success story. “They've shown how you can do this right--implementing it at a community level scale."