25 Years Ago
Today I Voted In The First All-Race Election In South Africa
It was a sunny and beautiful Friday morning
in the Port Elizabeth (South Africa) suburb of Saint Albans. It was a special
national holiday. All South Africans (regardless of race) were going to the
polls to elect a new president for the first time in the 500+ year history of
the country.
I was going through hard times
financially. I had a low-level clerical government job. I did not own a car. I
lived in a humble apartment with two other men. I only had a good diet because
my job was working at a center for military, police, and prison services
personnel. I got to eat in the officer’s mess. The food was quite decent.
Despite my humble circumstances, a
brand-new 3 Series BMW sedan pulled up at my apartment building. A well-dressed
captain in the South African army stepped out of the car. He walked to the door
of my apartment and knocked. When I opened the door, he told me that he had
been sent to take me to the polls to vote. (How I got this VIP treatment will
be the subject of a blog post tomorrow.)
I followed him to the BMW and got in on the
passenger side. There was great fear on this beautiful and sunny day. Major
violence and disruption had been predicted. As we drove through the streets of
Saint Albans, soldiers and police lined the streets. Despite all this tension,
there was a feeling of relaxation, hope, and confidence.
When we arrived at the polling place, the
captain came with me to the place where voters were checked in and given their
ballot. I presented my South African National ID book. The captain vouched for
me with election officials. I was given a two-page paper ballot. It had the
pictures of all candidates by the place to cast one’s vote. This was because so
many of the voters were illiterate and could not read and write.
I went to a polling station. I made my decision
and cast my vote. The captain drove me back to my apartment. Throughout South
Africa that day, there were sporadic and infrequent episodes of violence. No
charges were ever made of election tampering or voter fraud.
A little before midnight, Nelson Mandela was
declared the winner. There was euphoria all over South Africa. Parties were
going on everywhere. (Take my word for it, no one knows how to give a party
like South Africans!) For me the most touching moment of this election euphoria
was when a black woman was being interviewed on The South African Broadcasting
Commission. She said these words: “Finally they will start treating us like
adults and stop treating us like children!”
On that day I was part of an incredible
moment in history that was watched all over the world. I was honored to have
been allowed to vote. I was delighted to see a fair election with little
violence or intimidation. State President FW de Klerk conceded in a most-kind
manner.
I now have the benefit of 25 years to look
back on that day and what followed. Nelson Mandela went on to serve 5 years as
president. He exceeded all my expectations. The two men who came after him as
president were huge disappointments. At the time of the election 25 years ago,
South Africa was the economic power house of the African continent with 40% of
the continent’s gross domestic product. Now South Africa has the number three
economy in Africa with Nigeria being #1 and Egypt being #2.
Some progress has been made to alleviate
the huge disparity in comes and wealth that existed between the 15% white
minority and the 85% majority of color. The unemployment rate is still above
27%. Corruption is rampant. Crime rates are high. The new president, Cyril
Ramaphosa is honest and sincere. He has a hard challenge to overcome.
South Africa has not achieved what I had
hoped for it 25 years ago. But it is not a failed state either.
In praise of the mild-mannered Fresno chile, a California pepper waiting for its close-up
The chile looks a lot like a jalapeno and, well, it tastes like a jalapeno, too. But, you know, different. I first noticed it when I was eating the rice and beans at B.S. Taqueria downtown Los Angeles. The dish — the rice and beans — had a lot going on: The rice was puffed; the beans (white and garbanzos) were lightly fried. There were also grilled onions and cotija cheese, all served in a brown paper bag that quickly went wet with grease. But the chiles, they pulled the whole thing together, giving it a strange hint of sweetness, a tinge of smoke, and heat of course, a buzzy tingle and occasional pang. They never overwhelmed. They were very, very good. I was intrigued and, quickly, borderline obsessed. Why hadn’t I heard of a Fresno chile before?
Not long after that first encounter, I was talking to Ray Garcia, the chef-owner of B.S. Taqueria, who created the rice-and-bean dish. Fresnos are a “gateway chile,” he said — they’re friendly, easy to eat, both familiar and not. “People are like, ‘Oh! Fresnos! Yeah, I grow these! I grew up on these! This is, like, right before a jalapeno goes green, yeah?’” It is not. But it’s entirely possible you have encountered a Fresno, possibly in a supermarket, most likely mislabeled as a jalapeno. “No one knows what they’re talking about with Fresnos,” Garcia said, which seemed like it couldn’t be true. But, the more I looked into it, the more it turned out to be the case. Fresnos are right on the edge of familiarity: If you’d heard of them, you either had nothing to say about them, or what you did have to say was likely wrong. The chile was like the California city: a place you drove past and barely considered. Only, I wanted to consider it. I wasn’t even sure, starting out, if the city and the pepper had anything to do with each other.
They do. Sort of. Fresno chiles are named after Fresno, not the city, but the county in California’s central valley containing the city of the same name. They were developed in the 1950s by a local grower and seed merchant named Clarence “Brownie” Hamlin, who lived in the county of Fresno, in a town called Clovis, which is just outside the city of Fresno. The chile pepper Hamlin hybridized was, like all chile pepper plants, magnificently malleable. The chile pepper is a self-fertilizing plant, meaning the flowers on a single specimen contain both male and female genes. To crossbreed a pair of chiles, one plant has to be pollinated with the other. Swab the flower of one plant with a bee-like apparatus, perhaps a Q-tip, smear that across the flowers on the other plant, and boom, you’ve hybridized two peppers.
Okay, sure, it’s more complicated than that, since certain traits might show up in some peppers and not others, so there are seeds to save, and generations to cultivate, and traits to draw out through those generations, which is what Brownie Hamlin surely did to reach the variety he felt worth hanging onto and making an heirloom, the variety he named after the county he lived in and the town he lived near, the town at the center of the largest, most productive stretch of agricultural land on the continent, if not in the whole entire world.
Hamlin’s nephew, Casey, also lives near Fresno and sells seeds, including those of the Fresno, which he describes on his company’s website as similar to jalapenos but with thinner walls, which makes them perfect for cooking, or in a salsa. When I tried to buy the seeds online, or contact Casey directly, I couldn’t. Links were defunct, my calls and emails unreturned. I contacted the Fresno Historical Society, as well as the Fresno agricultural board, and, for good measure, the University of California’s agricultural cooperative, which has a few stations near Fresno. No one had anything to say about the Fresno chile.
Meanwhile, I began seeking out Fresnos everywhere I could, which produced all manner of disappointment. Unlike a jalapeno, serrano, Italian, shishito, or a bell pepper, a Fresno isn’t a regularly stocked item. You couldn’t plan around a Fresno, couldn’t count on it being there. And yet it is very much like those other far more common peppers, all of which are variations of the same species, capsicum annuum. (Not to be confused with black pepper, or piper nigrum, which comes from southern India.) All chile peppers come from the Americas — most likely central Mexico, where the plant was first cultivated at least 5,000 years ago.
Once the Spanish arrived, the peppers crossed oceans, first to Europe and then, carried by the Portuguese, to Asia, via the Indian port of Goa. Centuries passed, generation after generation of peppers: cultivated, hybridized, and folded into the cooking of regions throughout the globe. Peppers travel well and keep easily. The capsicum is a hearty plant, and the fruit works nearly every which way: grilled, sauteed, pickled, or dried and crushed. When looking at the great sweep of the chile pepper’s history, the Fresno is a very recent arrival. But that still doesn’t fully explain its second-class status. What might is its heat, or lack thereof.
Capsicums are unique plants — their fruit produces compounds called capsaicinoids, possibly, initially, evolutionarily, as a protective measure: to keep from being eaten. Capsaicinoids, you see, are what give the pepper its heat. The compounds aggravate and alarm our immune system. They make us feel hot and go sweaty. Humans, like peppers, are unique: Many of us find the experience of burning pain to be fantastic, excellent, delicious.
In recent decades, there has been a sort of arms race to hybridize ever-hotter peppers. In 1912, a Connecticut pharmacist named Wilbur Scoville developed the Scoville Organoleptic Test — a test for spiciness that involved progressive dilutions of a pepper’s extract into sugar water. The more dilutions required to minimize the heat to an imperceptible level, the hotter the pepper. And thus, the Scoville heat unit scale was born. A jalapeno requires about 5,000 parts water to one part chile extract to minimize its heat, so a jalapeno is around 5,000 Scoville heat units. A Fresno is about the same. A bell pepper is zero. The recently developed Bhut Jolokia is over a million SHUs. The Trinidad Scorpion is around 1.2 million. There is a very silly but also sort of fascinating debate as to which pepper is truly the hottest on Earth. On YouTube, there is a robust community of men (only men; mostly British) eating these peppers, going very red, weeping uncontrollably, falling on the floor, writhing, moaning, sweating, cursing, gasping, and bellowing. These are stunt peppers, not — if you are a sane and average person — for eating. The Fresno can’t compete.
Still, I wanted to track down some Fresnos, and find someone who could tell me something about them. I finally called Craig Underwood, a farmer who until recently grew all the jalapenos for Huy Fong Foods, Inc., makers of Sriracha, on 2,000 acres outside Ventura, California. He still grows jalapenos, as well as serranos and cascabels, but this year, he was putting in extra rows of Fresnos. “Way more than we’ve ever planted,” he yelled over the thrum of his pickup, piloting his way across his fields. His farm manager noticed that Fresnos were fetching pretty good prices down at LA’s 7th Street Produce Market, and Underwood wasn’t one to question what people wanted to buy. Maybe, he ventured, it was because in the fall, when the peppers turn red, their skin doesn’t crack the way a jalapeno’s often does. “People won’t buy a red jalapeno when it’s cracked,” he said with the confidence of a man whose trade is peppers. I asked Underwood if he thought there might be some growers still in Fresno, growing Fresnos. The community of pepper-growers in California was pretty small, he said, but he hadn’t heard of Brownie Hamlin or his nephew, and wasn’t sure about Fresnos growing in and around Fresno, which had lately turned to more lucrative crops, like almonds.
A few days after my call with Underwood, I decided to drive up to Fresno and find out for myself. Heading north from LA, up and over the San Emigdio Mountains, you first see the San Joaquin Valley from high above. If it’s early, which it was, clouds cling to the peaks as you drive by, and off in the distance, further east, nearly lost in the haze, are the Sierra Nevadas, still snowcapped in places, still holding the water that has fed this great valley since long before history, giving it some of the loamiest, richest soil on earth. The farmland begins even before the land levels out, continuing uninterrupted for some 450 miles. Fresno is smack in the middle. Some 85 percent of America’s carrots grow here, along with more than 90 percent of our raisins and almonds, around 95 percent of our processed tomatoes, and most of our walnuts, grapes, and pistachios, too. If you’re passing through the San Joaquin, you take I-5 (and, indeed, I usually do). But California State Route 99 cuts through the heart of the agricultural center and its cities. Driving the 99, it often seems like half the cars on the road are trucks laden with just-picked crops.
My first stop was a farm stand in Clovis, the town adjacent to Fresno and where Brownie Hamlin had first hybridized his chile seed. There I met Vincent Ricchiuti, great grandson of Vincenzo Ricchiuti, who first arrived in the Valley from Northern Italy in 1914. Vincent’s father, Patrick, runs P-R Farms, Inc., among the largest farming concerns in the valley. They grow peaches, plums, apricots, nectarines, apples, grapes, almonds, and olives. Vincent runs ENZO, an olive oil company; one of his olive oils is also made with crushed Fresno chiles. As it happened, he was just planting his field of Fresnos that morning, behind the building where he sold the oil.
Fresnos start the same as all the other peppers — after all, they’re technically the same plant, with different characteristics drawn out at different times in the life cycle. In Thai chiles, for example, the pepper begins green, as all peppers do. Then, the pepper turns a brownish color, and peaks in spiciness before eventually going red. Some recipes that call for Thai green peppers, or for Thai brown, or still others for Thai red — well, people think they are different peppers, but it’s the same exact pepper, just picked at different times throughout the season.
Across the street was a massive beige building, a packing plant for the family business. Behind the stand and store was a few acres of dirt, bounded on two sides by a housing development — enough space for nearly 11,000 chile plants. As we walked out toward the field, Ricchiuti described what it was that had drawn him to Fresnos, the only chile he used in any of his oils. He said that they were “nice and level” and “really approachable,” as well as “warm and inviting.” A spice that “doesn’t hit you in the face,” he said. Also, he added, his mother, “who does not like spice at all, puts it on her eggs all the time.” But the real reason he was planting all these Fresnos was because Fresnos had felt to him like a discovery, or a rediscovery — a re-evaluation of the place he was from and called home.
”It’s the most quintessential Fresno thing,” Ricchiuti said, squinting as he looked out over his field of chiles. “Here’s this beautiful food, named after us, but we’re not celebrating it, we don’t even know about it. It’s like a complex we’ve got: We’re not LA, we’re not San Francisco, and we’re reminded of that, often.” We walked along the rows of peppers for a stretch in silence. I had to admit, the plants didn’t look like much quite yet, just a few green shoots springing up out of the nearly black soil. “You got to go over to see Kong’s farm,” Ricchiuti said, breaking the silence. “That’s who got us set up here, because we’re not vegetable growers, really. But Kong, man, he’s growing the best vegetables in the country. I mean, Thomas Keller is flying his stuff to New York. Go see Kong. He’ll tell you what’s what. I think he’s got some Fresnos going in, too.”
An hour later, I arrived outside a small black gate, the entrance to Thao Family Farms, where Kong Thao met me and led me back to the 34 acres he and his parents and some of his 10 siblings farm. He smiled a rakish smile and asked if I was the guy who wanted to talk chiles, and then trudged off toward a patch of freshly tilled earth where his Fresnos had just gone in. “This is just a very small part of what we do,” he said, gesturing toward the patch. Beyond it were a dozen varieties of bell peppers, followed by dense rows of Italian long sweet peppers, Thai chiles, then arugula, tendrils of bitter melon, chards, collards, yu choy, bok choy, amaranth, blue spice basil, broccoli, Asian sorrel, Vietnamese coriander, chayote, several dozen varieties of heirloom tomatoes, 10 varieties of eggplant, six of summer squash, four of cucumbers — “a little bit of everything,” Thao said, eventually, giving up on listing it all.
Thao liked the Fresno chile’s complex flavor, but the reason he’d started growing it was even more basic than taste: “Vince and I, we’d been talking about it a few years, and finally we were like, ‘Let’s just do Fresnos, because we’re from Fresno.’” The taste of a pepper isn’t merely influenced by when it’s picked, but where it’s grown, so the Fresno has a different flavor when it’s grown in Fresno than anywhere elsewhere — farther north up the Valley, or along the coast, where growing seasons were longer. The peppers in those places get larger, but the flavor also gets diluted, according to Thao. In Fresno, the peppers were more compact, oily, and flavorful.
Thao mentioned a local chef named Jimmy Pardini, who also used his Fresnos, sometimes in salads, or on his pizzas. He came by the farm at least once a week to pick up some produce. It used to be, Thao would deliver directly to Pardini’s restaurant, the Annex Kitchen, but now Thao spends at least three days a week driving down to the farmer’s markets in Santa Monica, Hollywood, and Torrence, so he doesn’t have time anymore. Pardini was another one of the few locals who seemed to know about and like Fresno chiles. Maybe I should go talk to him?
Pardini’s restaurant was, as its name suggested, annexed from his family’s banquet hall and catering company, which they’d owned and operated for two generations. The space had been a diner — it still had the long counter with the kitchen right behind it, but now a pizza oven and huge wood grill dominated the entrance. A stack of almond wood from the Ricchiuti family orchards sat next to the grill. Fresno is a small place.
Like Thao and Ricchiuti, Pardini had grown up in Fresno, but he didn’t learn about Fresno chiles until after college, working the line at Osteria Mozza, Nancy Silverton’s LA restaurant. The pepper was in a linguine with clams. “I was like, ‘Fresno Fresno? Where I’m from? I know there’s, like, a Fresno in Mexico? Is that the town?’” It was hard to believe this pepper, showing up in this fancy restaurant in the big city, was from his humble home. It had to be something more exotic. But it wasn’t. It was Fresno, Fresno.
Later, I asked Silverton about the ways she uses the chile, what makes her like Fresnos as an ingredient, and what might have made Pardini first notice it. “Well it’s a beautiful chile, and when cooked there’s almost like a sweet kind of smoky note that it takes on,” she said. She slices it thin and chars it in the wood-burning oven and puts it on her salami pizza. Pickled, she adds it to braised chicken and sausage. Raw, she slices it into very thick rounds and, with a jalapeno, adds them to her spicy bean salad. There’s also a pesto she makes with Fresno chiles, for pasta.
The conversation turned to the Fresno’s provenance. She knew they were named after the city, but not much more than that. “It’s a newcomer, right?” Silverton ventured. Perhaps that was part of the problem, why it hadn’t found much of a foothold beyond chefs. It was new, as far as food goes. It didn’t have a tradition, or much of a story. “It’s a little lost soul,” she said, wistfully.
Pardini told me something similar, that although the pepper had a place, was named after a place, it kept falling through the cracks. “Each ethnic group has their chile,” he said. Italians long for the Italians, Armenian peppers for the Armenians, Thai chiles for the Thais, a whole universe of peppers for the Mexicans, he explained. In California, he continued, everyone had a friend — or an uncle, most likely — who had the peppers he grew in his backyard, the peppers he’d brag about over the grill in the summertime, and those peppers, passed down from generation to generation, were almost never Fresnos. We were, after all, a nation of immigrants, and peppers travel well. Even when a pepper came from here — even though all peppers come from this continent — we are loyal to the past, to the peppers we’ve known, that our ancestors had brought along.
But the Fresno chile can have a story, too. What’s nice about newcomers is that their story hasn’t been fully written, and can be yours to write. A few days after my trip to Fresno, I was at a nursery near my home, and there, beside the jalapenos and serranos, near the rows and rows of tomatoes, was a single Fresno chile plant in a tiny plastic pot. I took it up to the register, and the woman behind it couldn’t find the price anywhere. She thought it might have been a mistake, this plant’s arrival and existence in the nursery. That it had gotten mixed in with the other, more standard chiles. She sold it to me for a dollar and the next day, I planted it. There is at least one pepper growing on it now, small and green. But by the time you read this, maybe it will have started going red. And soon enough, it will be fall, and I’ll cut it open and carefully take out its seeds, saving them for next year. Then maybe I’ll pickle the rest of it, or make it into a jelly. I’ll have friends over to try some and I’ll probably tell them, yes, it comes from Fresno. But like all peppers it comes from elsewhere, too. It’s a hybrid. It’s a newbie. It’s a great American pepper. And isn’t it delicious?
A forensic artist recently reconstructed the face of a dog that lived around 4,500 years ago from a skull found in the Orkney Islands, off northern Scotland.
The artist used a 3D print from a scan of the animal’s cranium to reveal that the ancient canine resembled a European grey wolf and was the size of a large collie, Sky News reported.
The dog’s remains were found in a burial site called Cuween Hill in 1901. Researchers back then also discovered the remains of eight humans, suggesting that the dog was buried with its owners.
Steve Farrar, a manager with Historic Environment Scotland, which commissioned the reconstruction, said that Neolithic humans treasured their dogs, and trained them as guards and to tend sheep.
He also argued that the burial might have served a ritualistic purpose.
“Maybe dogs were their symbol or totem, perhaps they thought of themselves as the ‘dog people,'” he added.
Judging by the radiocarbon dating, the wolf-like pooch lived during a period when the Orkney Islands were one of the religious and cultural centers of Europe, and when Egyptians started building one of the seven wonders of the ancient world, the Great Pyramid of Giza.
I'm an ex-homeless person who celebrates 20 years out of homelessness (9/96-6/1999) on 4 July, 2019. I have empathy for these people. But I get upset that our city is being taken over by beaten-up vehicles, trailers, etc.
Most of us have had the misfortune at sometime on our life of sleeping in a vehicle at night. It gets very cold when the motor is turned-off. This is what these people in these vehicles suffer. We older people also have the challenge of having to go to the bathroom at 2:00 in the morning. If no bathroom is available, please use your imagination. What about showers? I swim over at Oceana Pool. One homeless married couple pays their dues and uses the pool for showers,etc. When I was homeless, I often had to go to the bathroom on the streets. I would sneak into buildings at 05:00 in the morning and use the basin to give myself a quick wash. Try to imagine the awful psychological pain of surviving with no electricity, water, internet or TV. Thank God for Life Moves (Inn Visions) that gave me shelter and hope. I would not have survived without them. Life Moves has excellent programs to help these people. Please talk to the Pacifica Resource Center about this incredible resources.
Respectfully, I feel that we need "a carrot and stick" approach. We need to let these people know that we will not tolerate their vehicles parked here. But,unlike other cities, we will not just push them out. We will guide them into programs through the Pacifica Resource Center, Life Moves, and other organizations like the VA (for veterans). They are going to have to "do it the hard way" and find jobs that pay them a living wage in this area. These jobs are available. I got an apartment with a $400 grant when I was surviving on $8.00 an hour exploitation jobs and working 16 hours a day. After three months in the apartment, I found a job paying $20.00 per hour. I stayed with that employer 8 years. I met and married Elena. The rest is history. I now have a nice home here in Pacifica and a good life. If I can do it. these other people can do it.
What have I learned in 70.5 years of life? I have learned many things. Most important is how we treat our fellow humans and animals. Pacifica needs to be the exception and work very hard to solve this problem in a humane manner without breaking the city budget.
Mike all of you on the City Council have a tough and thankless job. But it is a job that has to be done.
The public “Street Lifestyle” in the Bay Area is expanding and many of these people are looking for a new public parking space to move into and live without being cited or having to pay the cost of parking. Pacifica easily meets those requirements.
Pacifica is the new place to move into because the parking codes are very outdated and not keeping up with San Mateo County cities that saw this problem developing over the past two decades. Those cities protected their citizens with upgraded Municipal Parking Codes, not Pacifica.
New parking codes have not yet been approved by the Pacifica City Council for decades. New plans to approve upgraded parking codes are still being stalled and delayed by some city council members who don’t understand the risks they are causing to the City of Pacifica.
The “Health and Safety” risks for the citizens of Pacifica will continue and increase with the quantity of “RV’s” that are parked on the public streets.
The human health risks have been identified, as well as the environmental damages caused by this “Street Lifestyle”. The safety risks have also been identified by this transient lifestyle.
Reasonable human instincts and common sense can solve this problem. It is not as complex or difficult to solve as some people want it to be.
Who is our city insurance carrier? When the insurance carrier for the City of Pacifica finds out our codes are outdated, do they get to improve our “Health and Safety” with their opinion directed at the city council? We don’t want to loose our insurance carrier and we can’t afford to pay more for unhealthy and unsafe conditions.
The photographs included are from a Bay Area City that has people who are looking for new places to move. Maybe Pacifica is being considered?
Pacifica City Council, What happens now?
Desperate times call for desperate measures, goes the saying.
This might have been the case for the ancient Neanderthals in the south of France when they had to eat their own kind more than 120,000 years ago, Cosmos magazine reported.
In a study published in the Journal of Archaeological Science, researchers studied the bones of six Neanderthals found in a cave in southern France’s Rhone Valley, all bearing the trademarks of cannibalistic practices – cut marks caused by tools, dismemberment and gnawed fingerbones.
Researchers noted that the now-extinct early humans were living during the late interglacial period, an era of rapid warming that changed the flora and fauna of the region.
At that time, smaller rodents and reptiles started replacing the big game the ancient inhabitants hunted, which led to periods of malnutrition and sickness.
Eventually, they engaged in cannibalism to survive. But Neanderthal flesh wasn’t as nutritious as that of animals like deer, and hunting other humans would have been fruitless since only a few hundred inhabited western Europe at the time.
“They weren’t doing anything different to what modern humans would do in the same situation,” said archaeologist Michelle Langley, who was not involved in the study.
President Vladimir Putin unveiled ambitious plans to triple the size of Russia’s fleet of icebreakers and construct new ports on both sides of the Arctic shipping route in a bid to boost cargo shipments from last year’s 20 million tons to 80 million tons by 2025.
Addressing leaders from Finland, Iceland, Norway and Sweden at the Arctic forum in St. Petersburg, Putin said Russia is already building three nuclear icebreakers to add to its fleet of four, and plans to have 13 heavy icebreakers, including nine nuclear-powered ones, by 2035, the Associated Press reported.
That could put Moscow in pole position, so to speak, in the race to assert jurisdiction over parts of the Arctic as melting ice creates new opportunities for shipping and resource extraction, the agency noted.
Already, Russia has modernized a string of Soviet-era military bases to strengthen its hold on the region, which is estimated to hold up to one-quarter of the Earth’s undiscovered oil and gas. Meanwhile, other leaders at the forum spoke of the need to focus on areas of mutual interest to ensure peace and stability.
In a stunning piece of research, Stanford neuroscientists have hunted down a single gene that encodes a protein responsible for age-related cognitive losses, targeted it with special blocking antibodies, and shown in mice that these antibodies can rejuvenate old brains to work as well as young ones.
It all starts with the microglia, a class of brain cells responsible for immune responses and routine cleanup. Among many other functions, microglia spend their time gobbling up bits of protein deposits and cellular debris that result from normal brain activity, and it's long been known that their garbage-collecting performance deteriorates with age.
Tony Wyss-Coray, Ph.D, professor of neurology and neurological sciences at the Stanford University School of Medicine, thought it was a "decent bet" that the decline in microglial cleanup performance might be linked to the kinds of cognitive declines we see with aging. Both Alzheimer's and Parkinson's diseases, for example, are linked with abnormal activation patterns for genes associated with the microglia.
The hunt for a cognitive decline gene
So Wyss-Coray and his team set off on two concurrent lines of investigation. In one set of experiments, the team chose about 3,000 microglia-related genes they judged could be targeted with drugs. They filled Petri dishes with cultured mouse microglia cells, and gave them a flourescently-marked latex to chew on, and set about blocking those 3,000 genes one by one to see which ones made the microglia better or worse garbage eaters.
In another set of experiments, the team took the same 3,000 genes, and took measurements of each one's activity levels in young and old mice, looking for which genes changed their activity levels substantially with age.
And when they compared results between the two studies, expecting to find a long list of genes that both change microglial eating patterns and significantly change gene activity levels with age, they were stunned to find just one that fit both categories: a gene known as CD22 that's found in both mice and humans. They followed up and found the CD22 protein was three times as prevalent on the surface of old mice's microglia as on those of young mice.
Blocking the effects of CD22
With a possible culprit identified, the team set about blocking CD22 proteins using specially designed antibodies – ones that are too bulky to break through into cells, but can easily target cell-surface proteins. They injected these antibodies into one side of mice's hippocampuses, and for a control they injected a different antibody that couldn't bind with CD22 into the other side of the hippocampus.
This time, they used flourescence-labeled bits of myelin to track the brain halves' performance in scavenging waste – myelin being one of the microglia's chief scavenging targets, and also representing something that accumulates in aging brains. Sure enough, 48 hours later, there were far less of these myelin bits left on the side with the CD22-blocking antibodies. They tried the experiment again to see if the scavenging effect would be just as strong for Alzheimer's-related beta-amyloid and Parkinson's-related alpha-synuclein protein debris as it was for those bits of myelin. It was.
So by this stage the team had zeroed in on a gene protein that both decreases microglial scavenging performance and increases its activity with age. It had managed to block the activity of this gene, and shown that the administration of special antibodies could rejuvenate the ability of old brains to clean up a range of garbage proteins that begin to build up in older brains – ones heavily associated with serious cognitive illnesses. So how did these antibodies affect brain performance?
Turning back the hands of time
After a month of continuous CD22 antibody infusion on both sides of mice's brains, the researchers achieved a stunning result. The mice improved their performance on two different learning and memory tests to the point where they significantly outperformed control mice of the same age.
"The mice became smarter," says Wyss-Coray. "Blocking CD22 on their microglia restored their cognitive function to the level of younger mice. CD22 is a new target we think can be exploited for treatment of neurodegenerative diseases."
Stanford immediately rushed to file patents on IP related to the study. As always, it's much too early to get excited about the possibility of this research producing a fountain of youth-style drug that can let octogenarians enjoy the mental acuity of 25 year olds again. But the fact that CD22 is found in both the human and mouse genome certainly makes this a promising research area to keep an eye on.
The team's research appears in the journal Nature.
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