I told Newburg what Bode had said about it being so difficult and expensive to synthesize human-milk prebiotics.
“Hah!” said Newburg, baring a little professional rivalry. “We know how to do it. Come visit my lab. We’re up to our necks in shit.”
I know, most people would have declined this offer and fled. But by now I had fallen too far down the milky rabbit hole and was weirdly entranced by gut flora, that unexpected and invisible pillar of human health. I kept thinking of German’s image of us living at the behest of the microorganisms, not the other way around— “Who’s really cultivating whom?” he’d asked dramatically. The microflora outnumber us by a lot. There are ten times more microbacteria in our guts than there are cells in the human body. A song lyric kept playing in my head: Patty Griffin’s “You are not alone.”
And so, a few weeks later I was negotiating the steep, rainslicked steps outside of Higgins Hall on the Boston College campus. I maneuvered past a rather severe statue of St. Ignatius and into the new and immaculate molecular sciences building, where Newburg commands a spacious realm on the fourth floor.
Wearing black jeans, a black golf shirt, and sandals, Newburg welcomed me into his lab. It looked like a cross between a kitchen and a Kinko’s. The boxy, beige machines are actually mass spectrometer contraptions, such as the snazzy new “triple quad.” It sounds like a Vail chairlift and looks like a photocopier, but it costs around half a million dollars and breaks down molecules into gradually smaller components. To distinguish and identify different molecules, these machines utilize color, molecular weight, or, my favorite, “time of flight.” This one sends molecules pinging down a zigzag chamber and then up a small cylinder the size of a stovepipe. No two longchain molecules make the lap (or, technically, have the same mass-to-charge ratio) in exactly the same way. Many of the substances Newburg is finding in human milk have never been seen before.
The lab is a bank for two main kinds of substances: human diseases and the breast milk that fights them. To obtain the diseasecausing organisms, Newburg collects infant feces. He and his colleagues isolate the pathogens (such as botulinum, campylobacter, Vibrio cholerae, and Escherichia coli) and grow them in an anaerobic chamber similar to our guts. He especially treasures a source in Mexico, a clinic that sends him samples rich in things like rotavirus. Otherwise, he finds them through local hospitals and lactatingmom networks. “Just to handle baby poop is an incredibly long and complex process,” he said, involving informed-consent paperwork and hospital review boards. Some of his fecal freezers are set to –80 degrees Celsius, the temperature of outer space. Other incubators mimic body temperature for growing human cells from the lining of intestines and lungs (breast milk is also ferociously adept at fighting pneumonia). Leaving the tissue culture room, I saw a tube the size of a beer glass stuffed with what looks like raw steak. “That’s a liver,” said Newburg.
For him, analyzing baby shit is practical and urgent. Globally, 1.4 million children under five die each year from diarrheal illnesses. This makes sense if you consider that 20 percent of the world’s population doesn’t use any sort of toilet, and nearly half doesn’t have access to decent sanitation. Nearly a billion people don’t live near clean drinking water. At the same time, human milk is so effective at fighting infections that if all children were exclusively breast-fed the first six months of life, one in five childhood deaths could be prevented.
“Breast-fed poop doesn’t smell too obnoxious,” Newburg said. “It’s more like sour cheese or milk. Frankly, even as a guy, I got used to it.” Newburg led me to a normal-looking fridge to show off some of his precious collection, but he gasped when he saw the door was slightly ajar. A box of test tubes was wedged clumsily into the door. A small puddle had formed on the floor below it. “Oh no,” he said. A lab tech had accidently left the door open overnight. It occurred to me that the only thing worse than a freezer full of poop was a freezer full of thawing poop—especially for Newburg, who would have to deal with the scientific consequences. He lifted a test tube packed with brown goo and shook it. “I think this whole fridge is compromised,” he muttered.
After he washed his hands, we settled into his adjacent office for a chat. A poster-sized, soft-focus photograph of a blonde woman nursing a baby loomed above his desk (“My wife doesn’t like it,” he said of the image). Books such as Phospholipids Handbook, Gray’s Anatomy, and Modern Nutrition in Health and Disease packed the front wall. Like many men in this field, Newburg told me he didn’t start out intending to study lactation. His field was neuroscience. But running a rat experiment three decades ago, he noticed his formulafed pups “never performed as well as the nursed ones. A normal person would have said, ‘fine,’ but not me. I took a sabbatical to study essential nutrients for brain development,” and the rest is history.
He became intrigued by the indigestible oligosaccharides, and soon he had established that they must function to fight pathogens in the infant gut. In the 1980s, his lab (then at Harvard) rather startlingly discovered that human milk inhibits the transmission of HIV, among other things. He didn’t know exactly how, and he still doesn’t, although he’s closer to knowing which oligosaccharide compound is responsible. “We do know that the transmission of HIV through milk is much less than through any other medium,” he said. He fully expects to identify the heroic sugar complex, then make it and offer it up as a therapy in the real world. “We’ll study it and we’ll find out,” he said. “It would be much more effective than a vaccine, I think.”
Already, Newburg’s company, Glycosyn (he cofounded it in 2002), is making a “2-linked fucosyloligosaccharide” known to help ward off norovirus, E. coli, cholera, and campylobacter. Because, as Bode pointed out, it’s too expensive to synthesize these molecules from scratch, Newburg has a different strategy. He’s teaching yeast to produce them for him by converting a natural product they make into a building block called fucose. He then takes that and links it to lactose “because that’s what mom does.” Some other companies in Europe are making oligosaccharides from plants or cow’s milk and putting them in infant food, but Newburg says it’s not the same.
Glycosyn will start testing its product in humans sometime in 2012 or 2013. Newburg told me the final product will probably resemble a sugar packet that can be mixed into food or formula. It will be ideal for babies on formula or babies and toddlers who are weaning, which can be a treacherous process in developing countries with unsafe food and water. Newburg’s product will be like NutraSweet for the survival set, the mysterious stuff of breasts purified into a paper packet.
As someone who extols the benefits of breast milk but wants to improve formula, Newburg has garnered some criticism from both sides. If there’s one thing the lactivists hate, it’s better formula, because they think it can never really be good enough. “It’s frustrating to see moms who don’t breast-feed, but I understand why some don’t,” said Newburg. “I don’t think their children should be punished. My orientation is to the baby.”
LECHISTAS, PREPARE YOURSELVES: FORMULA WILL GET BETTER and so will a bunch of other foods, supplements, therapies, and medications thanks to the unlocked secrets of milk. A quick survey of what other biotech companies are doing shows the range of benefits being urgently, greedily, attributed to human milk. It’s important to remember from chapter 2 that lactation likely evolved from the immune system; its primary function was not nutrition but protection. Most of the cells in milk are macrophages, which disable viruses, fungi, and bacteria. I already mentioned Prolacta Bioscience, which is concentrating and pasteurizing donated human milk—and then selling it—as an “immunonutrition” supplement for preemies weighing less than 2.5 pounds. In the Brave New World department, several companies are reengineering other animals to produce the unique ingredients of human milk, because it’s still easier and cheaper to raise a herd of transgenic goats than it is to beg or buy large quantities of milk from suburban mothers.
One of the most sought-after components of human milk
is a glycoprotein called lactoferrin. Known to have keen anti-inflammation, antioxidant, and anti-infective properties, it’s an iron-binding machine that outcompetes pathogens. Lactoferrin can also be found in tears and saliva and genital secretions, but in tiny percentages compared to milk. It’s possible to inject animal embryos with the human gene that makes it. Some companies are genetically altering cows, goats, and even rabbits, then isolating the human lactoferrin from the milk. One Japanese company has begun marketing capsules, which it calls “Lactoferrin Gold.” Three liters of modified cow’s milk are needed to make one capsule. I can see why they named it after a precious ore. To make lactoferrin, another company bred a whole herd of cows from one long-dead transgenic bull named Herman. But altered mold fungus can make it too. A biotech outfit with over a hundred lactoferrin patents intends to use the fungal product for fighting cancer and healing wounds.
According to one economic analysis, if lactoferrin were added to infant formula, it would create an extra $15 billion in value. If added to eye drops, oral hygiene, soaps, and shampoos, another $10 billion. Cancer drugs: $19 billion.
That’s just lactoferrin, but there is also active research on other components. Stem cells, for example, teem from human milk, particularly from the dense colostrum produced in the early days of nursing. Before the baby is five days old, she’ll receive five million stem cells from the mother. No one really knows why. Are they colonizing the baby in case she needs them? Are they just a by-product from the newly functional mammary gland? Then there’s a very cool protein called alpha-lactalbumin. In the acids of the infant stomach, the protein refolds itself and picks up a neighboring fatty acid, also from the milk, forming a new complex. The scientist who discovered it fifteen years ago, a Swede named Catharina Svanborg, dubbed it HAMLET, for human alpha-lactalbumin made lethal to tumor cells.
This HAMLET ditches the pretty soliloquys and dons a superhero cape, diving into the nuclei of malignant (and viral) cells and freezing the gears. It effectively prevents malignant DNA from replicating and then in a final grand stage gesture causes the cells to implode. Weirdly and auspiciously, it seems to destroy only bad cells, leaving the good ones alone. Laboratory experiments have shown that HAMLET kills forty different types of cancer cells in a dish, including those of the bladder, lymphoma, skin, and brain, but it has not been tested much in humans yet. Still, the reason Svanborg began looking at milk is that several studies found that formula-fed children have significantly higher rates of childhood lymphoma than their breast-fed peers.
All this ought to make nursing mothers feel a little more valuable. Maybe they’ll wise up and start registering with insurance companies as health-care providers. Or maybe they’ll join the rawmilk underground. A few already have: an Internet site called Only The Breast lists classifieds with wording like “scrumptious mommy milk.” At four dollars per ounce, it costs 262 times the price of a barrel of oil. The marketplace for human milk in most of the United States and in the rest of the world is unregulated so far, despite the fact that it’s capable of transmitting hepatitis and other maternal diseases along with lactoferrin. Nonprofit human milk banks (there are eleven in North America) heat the milk to pasteurize it, but the process also kills some of its bioactive ingredients. While donor milk is used mostly in neonatal intensive care units for preemies, older children and adults sometimes buy it for treating various illnesses or for soothing the harsh mucosal effects of chemotherapy.
As Bruce German had reminded me in Peru, these breakthroughs in the understanding of milk are not just interesting; they are fundamentally altering what we know about human health. “The story that is compelling to me is the fascinating interplay between bacteria and humans,” he’d said. “This whole story is part of a revolution in science itself, where the chemistry-dominated science of the twentieth century is giving way to the biology-dominated science of the twenty-first century. Such a shift is sometimes difficult to appreciate, especially for people outside the scientific community. For milk and bacteria there is an easy point of entry for people to see the vivid contrast: twentieth-century chemistry—use chemicals to kill all bacteria; twenty-first century—use biomolecules and organisms to guide a supportive microbial ecology. It’s a new world of science.”
NATURE HAS DESIGNED MILK TO BE INGENIOUS, BUT IT’S THE breast itself that directs the show. Biologists bat around the concept of “crosstalk,” how one part of the body communicates with another and vice versa. In the case of the lactating breast, the organ is communicating not only with its immediate landlady but also with the infant. From the very beginning, the breast appears to know whether the infant is a boy or a girl, at least in rhesus macaque monkeys, which have similar milk to humans and have been studied more comprehensively than their human relatives. In the macaques, mothers of sons produced fatter, more-energy-dense milk. Katherine Hinde, a professor in the human evolutionary biology department at Harvard University, thinks this might be because macaque males have slightly higher growth rates and as adults weigh about 30 percent more than females (human males weigh about 15 percent more than females). But Hinde has another, more devious social theory as well. She discovered that macaque mothers produce fattier milk for sons, but they make more milk for daughters, meaning the maternal energy investment is about the same. In that matrilineal primate society, daughters learn from hanging around their mothers longer and more often, and thinner milk means they stay close for more frequent feedings. The sons, by contrast, might be “tricked” by the mother’s fattier milk into feeling sated and therefore not feeding as often. It’s not a bad thing for the sons; they have more time to play and explore, skills they’ll need down the road when they leave the group.
How does the breast know whether the infant is male or female? Probably because hormones called placental lactogens talk to the breast during pregnancy, when it is building the structures it will need for making milk. Girls evidently get the skim-milk machinery. Mom wants to produce good milk, but she doesn’t want to kill herself doing it, which brings up an interesting dynamic between mother and infant: competition. Babies have evolved their own tricks to get as much of their mother’s resources as they can: Witness the tightly interwoven placenta (made by the embryo) that becomes essentially parasitic. The mother’s body has genes to expel the fetus a little before the due date. The baby’s genes—put there by the father, presumably—tell it to stay put a little longer.
The breast picks up the tug-of-war after birth, slipping endocannabinoids into the milk. Note the root cannabis in there. These substances, which cause the munchies, probably play a role in enticing infants to eat. But they also regulate appetite so infants feel very full by the end of a feed and thus don’t eat too much. Interestingly, formula lacks these compounds, and formula-fed babies have a notoriously higher caloric intake. It’s one of the speculations about why we have a childhood obesity epidemic.
While looking out for the mother, the breast is also looking out for the baby. It is constantly sussing out his or her nutritional and immunological needs. When the breast senses an infection brewing in the baby, it somehow tips off the mother’s immune system and in turn the milk puts out more lactoferrin and the relevant antibodies. When the baby is older than one year, the milk contains more fat and cholesterol to match the baby’s energy needs. When a baby is born prematurely, the mother’s milk, as if anticipating its role, contains more protein and caloric density for a tiny tummy. Is it a coincidence or did we evolve that way, despite the unlikelihood that many preemies survived in our early history?
The breast is like a smartphone and juice bar in one. It communicates with the mother’s body, the baby’s body, and the environment. The breast knows the condition of the mother. Stress, for example, can cause her to hold back her output of milk. It can also send more cortisol into the milk, which appears to affect the longterm personality of sons (but not necessarily daughters), perhaps making them more exploratory or hypervigilant to grow up in a difficult environment. We know th
at a tough environment can affect a mother’s stress levels. After the terrorist attacks of 9/11, many new mothers all over the country experienced temporary problems producing enough breast milk. My son was eight weeks old. Looking back, I wonder if this event played a role in our early difficulties with supply and demand. Unlike my mother, though, I never kept a nursing log.
Cells in the breast communicate with cells in the bone, telling the bone how much calcium to release for milk production and when to start guarding it again. A mother loses up to 6 percent of her calcium for her baby, but the stock more than fully replenishes within a few months after weaning. In terms of things like energy and minerals, breast-feeding takes a severe toll on mothers, though not as severe as the toll of gestating and delivering a fetus. Breast-feeding actually helps the mother recover from these events by tweaking her metabolism and protecting her heart. It’s a critical part of how the enterprise was designed for our benefit as well as our baby’s.
Internist and researcher Eleanor Schwarz had told a story in Peru about her inspiration for a study. “I was storing some of my milk in bottles in the refrigerator, and I noticed it looked like buttermilk,” she’d recalled. “That’s how fatty it is. Was there some relationship between the bottle of butter I was storing in the fridge and my future cardiovascular risk?” In other words, was the fact that her body was mobilizing her fat and siphoning it into milk helpful to her arteries or not? Some studies had shown that women who breast-feed lose more pregnancy weight than mothers who don’t, but the data were inconsistent, and there wasn’t much information about types of fat they lose or where it came from in their bodies.
Breasts Page 17