Jamie Rettinger with his now fiance Amie Purnel-Davis, who helped him through the clinical trial.
Melanoma is the deadliest form of skin cancer. About 85,000 people are diagnosed with it each year in the U.S. and more than 8,000 die of the cancer when it spreads to other parts of the body, according to the Centers for Disease Control and Prevention (CDC).
There are two peaks in diagnosis of melanoma; one is in younger women ages 30-40 and often is tied to past use of tanning beds; the second is older men 60+ and is related to outdoor activity from farming to sports. Light-skinned people have a twenty-times greater risk of melanoma than do people with dark skin.
"When I graduated from medical school, in 2005, melanoma was a death sentence" --Diwakar Davar.
Jamie had a follow up PET scan about six months after his surgery. A suspicious spot on his lung led to a biopsy that came back positive for melanoma. The cancer had spread. Treatment with a monoclonal antibody (nivolumab/Opdivo®) didn't prove effective and he was referred to the UPMC Hillman Cancer Center in Pittsburgh, a four-hour drive from his home in western Ohio.
An alternative monoclonal antibody treatment brought on such bad side effects, diarrhea as often as 15 times a day, that it took more than a week of hospitalization to stabilize his condition. The only options left were experimental approaches in clinical trials.
Early research
"When I graduated from medical school, in 2005, melanoma was a death sentence" with a cure rate in the single digits, says Diwakar Davar, 39, an oncologist at UPMC Hillman Cancer Center who specializes in skin cancer. That began to change in 2010 with introduction of the first immunotherapies, monoclonal antibodies, to treat cancer. The antibodies attach to PD-1, a receptor on the surface of T cells of the immune system and on cancer cells. Antibody treatment boosted the melanoma cure rate to about 30 percent. The search was on to understand why some people responded to these drugs and others did not.
At the same time, there was a growing understanding of the role that bacteria in the gut, the gut microbiome, plays in helping to train and maintain the function of the body's various immune cells. Perhaps the bacteria also plays a role in shaping the immune response to cancer therapy.
One clue came from genetically identical mice. Animals ordered from different suppliers sometimes responded differently to the experiments being performed. That difference was traced to different compositions of their gut microbiome; transferring the microbiome from one animal to another in a process known as fecal transplant (FMT) could change their responses to disease or treatment.
When researchers looked at humans, they found that the patients who responded well to immunotherapies had a gut microbiome that looked like healthy normal folks, but patients who didn't respond had missing or reduced strains of bacteria.
Davar and his team knew that FMT had a very successful cure rate in treating the gut dysbiosis of Clostridioides difficile, a persistant intestinal infection, and they wondered if a fecal transplant from a patient who had responded well to cancer immunotherapy treatment might improve the cure rate of patients who did not originally respond to immunotherapies for melanoma.
The ABCDE of melanoma detection
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Clinical trial
"It was pretty weird, I was totally blasted away. Who had thought of this?" Jamie first thought when the hypothesis was explained to him. But Davar's explanation that the procedure might restore some of the beneficial bacterial his gut was lacking, convinced him to try. He quickly signed on in October 2018 to be the first person in the clinical trial.
Fecal donations go through the same safety procedures of screening for and inactivating diseases that are used in processing blood donations to make them safe for transfusion. The procedure itself uses a standard hollow colonoscope designed to screen for colon cancer and remove polyps. The transplant is inserted through the center of the flexible tube.
Most patients are sedated for procedures that use a colonoscope but Jamie doesn't respond to those drugs: "You can't knock me out. I was watching them on the TV going up my own butt. It was kind of unreal at that point," he says. "There were about twelve people in there watching because no one had seen this done before."
A test two weeks after the procedure showed that the FMT had engrafted and the once-missing bacteria were thriving in his gut. More importantly, his body was responding to another monoclonal antibody (pembrolizumab/Keytruda®) and signs of melanoma began to shrink. Every three months he made the four-hour drive from home to Pittsburgh for six rounds of treatment with the antibody drug.
"We were very, very lucky that the first patient had a great response," says Davar. "It allowed us to believe that even though we failed with the next six, we were on the right track. We just needed to tweak the [fecal] cocktail a little better" and enroll patients in the study who had less aggressive tumor growth and were likely to live long enough to complete the extensive rounds of therapy. Six of 15 patients responded positively in the pilot clinical trial that was published in the journal Science.
Davar believes they are beginning to understand the biological mechanisms of why some patients initially do not respond to immunotherapy but later can with a FMT. It is tied to the background level of inflammation produced by the interaction between the microbiome and the immune system. That paper is not yet published.
Surviving cancer
It has been almost a year since the last in his series of cancer treatments and Jamie has no measurable disease. He is cautiously optimistic that his cancer is not simply in remission but is gone for good. "I'm still scared every time I get my scans, because you don't know whether it is going to come back or not. And to realize that it is something that is totally out of my control."
"It was hard for me to regain trust" after being misdiagnosed and mistreated by several doctors he says. But his experience at Hillman helped to restore that trust "because they were interested in me, not just fixing the problem."
He is grateful for the support provided by family and friends over the last eight years. After a pause and a sigh, the ruggedly built 47-year-old says, "If everyone else was dead in my family, I probably wouldn't have been able to do it."
"I never hesitated to ask a question and I never hesitated to get a second opinion." But Jamie acknowledges the experience has made him more aware of the need for regular preventive medical care and a primary care physician. That person might have caught his melanoma at an earlier stage when it was easier to treat.
Davar continues to work on clinical studies to optimize this treatment approach. Perhaps down the road, screening the microbiome will be standard for melanoma and other cancers prior to using immunotherapies, and the FMT will be as simple as swallowing a handful of freeze-dried capsules off the shelf rather than through a colonoscopy. Earlier this year, the Food and Drug Administration approved the first oral fecal microbiota product for C. difficile, hopefully paving the way for more.
An older version of this hit article was first published on May 18, 2021
Overabundance of dissolved carbon dioxide poses a threat to marine life. A new system detects elevated levels of the greenhouse gases and mitigates them on the spot.
To date, though, methods for measuring CO2 in water at scale have been either intensely expensive, requiring fancy sensors that pump CO2 through membranes; or prohibitively complicated, involving a series of lab-based analyses. And that’s led to a bottleneck in efforts to remove carbon as well.
But recently, Boudinot cracked part of the code for measurement and mitigation, at least on a small scale. While the rest of the industry sorts out larger intricacies like getting ocean carbon markets up and running and driving carbon removal at billion-ton scale in centralized infrastructure, his decentralized method could have important, more immediate implications.
Specifically, for shellfish hatcheries, which grow seafood for human consumption and for coastal restoration projects. Some of these incubators for oysters and clams and scallops are already feeling the negative effects of excess carbon in water, and Vycarb’s tech could improve outcomes for the larval- and juvenile-stage mollusks they’re raising. “We’re learning from these folks about what their needs are, so that we’re developing our system as a solution that’s relevant,” Boudinot says.
Ocean acidification can wreak havoc on developing shellfish, inhibiting their shells from growing and leading to mass die-offs.
Ocean waters naturally absorb CO2 gas from the atmosphere. When CO2 accumulates faster than nature can dissipate it, it reacts with H2O molecules, forming carbonic acid, H2CO3, which makes the water column more acidic. On the West Coast, acidification occurs when deep, carbon dioxide-rich waters upwell onto the coast. This can wreak havoc on developing shellfish, inhibiting their shells from growing and leading to mass die-offs; this happened, disastrously, at Pacific Northwest oyster hatcheries in 2007.
This type of acidification will eventually come for the East Coast, too, says Ryan Wallace, assistant professor and graduate director of environmental studies and sciences at Long Island’s Adelphi University, who studies acidification. But at the moment, East Coast acidification has other sources: agricultural runoff, usually in the form of nitrogen, and human and animal waste entering coastal areas. These excess nutrient loads cause algae to grow, which isn’t a problem in and of itself, Wallace says; but when algae die, they’re consumed by bacteria, whose respiration in turn bumps up CO2 levels in water.
“Unfortunately, this is occurring at the bottom [of the water column], where shellfish organisms live and grow,” Wallace says. Acidification on the East Coast is minutely localized, occurring closest to where nutrients are being released, as well as seasonally; at least one local shellfish farm, on Fishers Island in the Long Island Sound, has contended with its effects.
The second Vycarb pilot, ready to be installed at the East Hampton shellfish hatchery.
Courtesy of Vycarb
Besides CO2, ocean water contains two other forms of dissolved carbon — carbonate (CO3-) and bicarbonate (HCO3) — at all times, at differing levels. At low pH (acidic), CO2 prevails; at medium pH, HCO3 is the dominant form; at higher pH, CO3 dominates. Boudinot’s invention is the first real-time measurement for all three, he says. From the dock at the Navy Yard, his pilot system uses carefully calibrated but low-cost sensors to gauge the water’s pH and its corresponding levels of CO2. When it detects elevated levels of the greenhouse gas, the system mitigates it on the spot. It does this by adding a bicarbonate powder that’s a byproduct of agricultural limestone mining in nearby Pennsylvania. Because the bicarbonate powder is alkaline, it increases the water pH and reduces the acidity. “We drive a chemical reaction to increase the pH to convert greenhouse gas- and acid-causing CO2 into bicarbonate, which is HCO3,” Boudinot says. “And HCO3 is what shellfish and fish and lots of marine life prefers over CO2.”
This de-acidifying “buffering” is something shellfish operations already do to water, usually by adding soda ash (NaHCO3), which is also alkaline. Some hatcheries add soda ash constantly, just in case; some wait till acidification causes significant problems. Generally, for an overly busy shellfish farmer to detect acidification takes time and effort. “We’re out there daily, taking a look at the pH and figuring out how much we need to dose it,” explains John “Barley” Dunne, director of the East Hampton Shellfish Hatchery on Long Island. “If this is an automatic system…that would be much less labor intensive — one less thing to monitor when we have so many other things we need to monitor.”
Across the Sound at the hatchery he runs, Dunne annually produces 30 million hard clams, 6 million oysters, and “if we’re lucky, some years we get a million bay scallops,” he says. These mollusks are destined for restoration projects around the town of East Hampton, where they’ll create habitat, filter water, and protect the coastline from sea level rise and storm surge. So far, Dunne’s hatchery has largely escaped the ill effects of acidification, although his bay scallops are having a finicky year and he’s checking to see if acidification might be part of the problem. But “I think it's important to have these solutions ready-at-hand for when the time comes,” he says. That’s why he’s hosting a second, 70-liter Vycarb pilot starting this summer on a dock adjacent to his East Hampton operation; it will amp up to a 50,000 liter-system in a few months.
If it can buffer water over a large area, absolutely this will benefit natural spawns. -- John “Barley” Dunne.
Boudinot hopes this new pilot will act as a proof of concept for hatcheries up and down the East Coast. The area from Maine to Nova Scotia is experiencing the worst of Atlantic acidification, due in part to increased Arctic meltwater combining with Gulf of St. Lawrence freshwater; that decreases saturation of calcium carbonate, making the water more acidic. Boudinot says his system should work to adjust low pH regardless of the cause or locale. The East Hampton system will eventually test and buffer-as-necessary the water that Dunne pumps from the Sound into 100-gallon land-based tanks where larvae grow for two weeks before being transferred to an in-Sound nursery to plump up.
Dunne says this could have positive effects — not only on his hatchery but on wild shellfish populations, too, reducing at least one stressor their larvae experience (others include increasing water temperatures and decreased oxygen levels). “If it can buffer water over a large area, absolutely this will [benefit] natural spawns,” he says.
No one believes the Vycarb model — even if it proves capable of functioning at much greater scale — is the sole solution to acidification in the ocean. Wallace says new water treatment plants in New York City, which reduce nitrogen released into coastal waters, are an important part of the equation. And “certainly, some green infrastructure would help,” says Boudinot, like restoring coastal and tidal wetlands to help filter nutrient runoff.
In the meantime, Boudinot continues to collect data in advance of amping up his own operations. Still unknown is the effect of releasing huge amounts of alkalinity into the ocean. Boudinot says a pH of 9 or higher can be too harsh for marine life, plus it can also trigger a release of CO2 from the water back into the atmosphere. For a third pilot, on Governor’s Island in New York Harbor, Vycarb will install yet another system from which Boudinot’s team will frequently sample to analyze some of those and other impacts. “Let's really make sure that we know what the results are,” he says. “Let's have data to show, because in this carbon world, things behave very differently out in the real world versus on paper.”
Many children use makeup and body products such as glitter, face paint and lip gloss. Scientists are pointing to the harmful chemicals in some of these products, and advocates are looking to outlaw them.
In 2013, Toxic-Free Future launched Mind the Store to challenge the nation’s largest retailers in adopting comprehensive policies that eliminate toxic chemicals in their personal care products and packaging, and develop safer alternatives.
Now, more efforts are underway to expose and mitigate the harm in cosmetics, hair care and other products that children apply on their faces, heads, nails and other body parts. Advocates hope to raise awareness among parents while prompting manufacturers and salon professionals to adopt safer alternatives.
A recent study by researchers at Columbia University Mailman School of Public Health and Earthjustice, a San Francisco-based nonprofit public interest environmental law organization, revealed that most children in the United States use makeup and body products that may contain carcinogens and other toxic chemicals. In January, the results were published in the International Journal of Environmental Research and Public Health. Based on more than 200 surveys, 70 percent of parents in the study reported that their children 12 or younger have used makeup and body products marketed to youth — for instance, glitter, face paint and lip gloss.
Childhood exposure to harmful makeup and body product ingredients can also be considered an environmental justice issue, as communities of color may be more likely to use these products.
“We are concerned about exposure to chemicals that may be found in cosmetics and body products, including those that are marketed toward children,” said the study’s senior author, Julie Herbstman, a professor and director of the Columbia Center for Children's Environmental Health. The goal of the survey was to try to understand how much kids are using cosmetic and body products and when, how and why they are using them.
“There is widespread use of children’s cosmetic and body products, and kids are using them principally to play,” Herbstman said. “That’s really quite different than how adults use cosmetic and body products.” Even with products that are specifically designed for children, “there’s no regulation that ensures that these products are safe for kids.” Also, she said, some children are using adult products — and they may do so in inadvisable ways, such as ingesting lipstick or applying it to other areas of the face.
Earlier research demonstrated that beauty and personal care products manufactured for children and adults frequently contain toxic chemicals, such as lead, asbestos, PFAS, phthalates and formaldehyde. Heavy metals and other toxic chemicals in children’s makeup and body products are particularly harmful to infants and youth, who are growing rapidly and whose bodies are less efficient at metabolizing these chemicals. Whether these chemicals are added intentionally or are present as contaminants, they have been associated with cancer, neurodevelopmental harm, and other serious and irreversible health effects, the Columbia University and Earthjustice researchers noted.
“Even when concentrations of individual chemicals are low in products, the potential for interactive effects from multiple toxicants is important to take into consideration,” the authors wrote in the journal article. “Allergic reactions, such as contact dermatitis, are some of the most frequently cited negative health outcomes associated with the use of cosmetics.”
Children’s small body side, rapid growth rate and immature immune systems are biologically more prone to the effects of toxicants than adults.
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In addition to children’s rapid growth rate, the study also reported that their small body size, developing tissues and organs, and immature immune systems are biologically more prone to the effects of toxicants than adults. Meanwhile, the study noted, “childhood exposure to harmful makeup and body product ingredients can also be considered an environmental justice issue, as communities of color may be more likely to use these products.”
Although adults are the typical users of cosmetics, similar items are heavily marketed to youth with attention-grabbing features such as bright colors, animals and cartoon characters, according to the study. Beyond conventional makeup such as eyeshadow and lipstick, children may apply face paint, body glitter, nail polish, hair gel and fragrances. They also may frequent social media platforms on which these products are increasingly being promoted.
Products for both children and adults are currently regulated by the U.S. Food and Drug Administration under the Federal Food, Drug, and Cosmetic Act of 1938. Also, the Fair Packaging and Labeling Act of 1967 directs the Federal Trade Commission and the FDA “to issue regulations requiring that all ‘consumer commodities’ be labeled to disclose net contents, identity of commodity, and name and place of business of the product's manufacturer, packer, or distributor.” As the Columbia University and Earthjustice authors pointed out, though, “current safety regulations have been widely criticized as inadequate.”
The Personal Care Products Council in Washington, D.C., “fundamentally disagrees with the premise that companies put toxic chemicals in products produced for children,” industry spokeswoman Lisa Powers said in an email. Founded in 1894, the national trade association represents 600 member companies that manufacture, distribute and supply most personal care products marketed in the United States.
No category of consumer products is subject to less government oversight than cosmetics and other personal care products. -- Environmental Working Group.
“Science and safety are the cornerstones of our industry,” Powers stated. For more than a decade, she wrote, “the [Council] and our member companies worked diligently with a bipartisan group of congressional leaders and a diverse group of stakeholders to enhance the effectiveness of the FDA regulatory authority and to provide the safety reassurances that consumers expect and deserve.”
Powers added that the “industry employs and consults thousands of scientific and medical experts” who study the impacts of cosmetics and personal care products and the ingredients used in them. The Council also maintains a comprehensive database where consumers can look up science and safety information on the thousands of ingredients in sunscreens, toothpaste, shampoo, moisturizer, makeup, fragrances and other products.
However, the Environmental Working Group, which empowers consumers with breakthrough research to make informed choices about healthy living, believes the regulations are still not robust enough. “No category of consumer products is subject to less government oversight than cosmetics and other personal care products,” states the organization’s website. “Although many of the chemicals and contaminants in cosmetics and personal care products likely pose little risk, exposure to some has been linked to serious health problems, including cancer.”
The group, which operates the Skin Deep Database noted that “since 2009, 595 cosmetics manufacturers have reported using 88 chemicals, in more than 73,000 products, that have been linked to cancer, birth defects or reproductive harm.”
But change, for both adults and kids, is on the horizon. The Modernization of Cosmetics Regulation Act of 2022 significantly expanded the FDA’s authority to regulate cosmetics. In May 2023, Washington state adopted a law regulating cosmetics and personal care products. The Toxic-Free Cosmetics Act (HB 1047) bans chemicals in beauty and personal care products, such as PFAS, lead, mercury, phthalates and formaldehyde-releasing agents. These bans take effect in 2025, except for formaldehyde releasers, which have a phased-in approach starting in 2026.
Industry and advocates view this as a positive development. Powers, the spokesperson, praised “the long-awaited” Modernization Cosmetics Regulation Act of 2022, which she said, “advances product safety and innovation.” Jen Lee, chief impact officer at Beautycoutner, a company that sells personal care products, also welcomes the change. “We were proud to support the Washington Toxic-Free Cosmetics Act (HB 1047) by mobilizing our community of Brand Advocates who reside in Washington State,” Lee said. “Together, they made their voices heard by sending over 1,000 emails to their state legislators urging them to support and pass the bill.”
Laurie Valeriano, executive director of Toxic-Free Future, praised the upcoming Washington state law as “a huge win for public health and the environment that will have impacts that ripple across the nation.” She added that “companies won’t make special products for Washington state.” Instead, “they will reformulate and make products safer for everyone” — adults and children.
You shouldn’t have to be a toxicologist to shop for shampoo. -- Washington State Rep. Sharlett Mena
The new legislation will require Washington state agencies to assess the hazards of chemicals used in products that can impact vulnerable populations, while providing support for small businesses and independent cosmetologists to transition to safer products.
The Toxic-Free Future team lauds the Cosmetics Act, signed in May 2023.
Courtesy Toxic-Free Future
“When we go to a store, we assume the products on the shelf are safe, but this isn’t always true,” said Washington State Rep. Sharlett Mena, a Democrat serving in the 29th Legislative District (Tacoma), who sponsored the law. “I introduced this bill (HB 1047) because currently, the burden is on the consumer to navigate labels and find safe alternatives. You shouldn’t have to be a toxicologist to shop for shampoo.”
The new law aims to protect people of all ages, but especially youth. “Children are more susceptible to the impacts of toxic chemicals because their bodies are still developing,” Mena said. “Lead, for example, is significantly more hazardous to children than adults. Also, since children, unlike adults, tend to put things in their mouths all the time, they are more exposed to harmful chemicals in personal care and other products.”
Cosmetologists and hair professionals are taking notice. “Safety should be the practitioner’s number one concern” in using products on small children, said Anwar Saleem, a hair stylist, instructor and former salon owner in Washington, D.C., who is chairman of the D.C. Board of Barbering and Cosmetology and president of the National Interstate Council of State Boards of Cosmetology. “There are so many products on the market that it can be confusing.”
Hair products designed and labeled for children's use often have milder formulations, but “every child is unique, and what works for one may not work for another,” Saleem said. He recommends doing a patch test, in which the stylist or cosmetologist dabs the product on a small, inconspicuous area of the scalp or skin and waits anywhere from an hour to a day to check for irritation before continuing to serve the client. “Performing a patch test, observing children's reactions to a product and adequately adjusting are essential.”
Saleem seeks products that are free from harsh chemicals such as sulfates, phthalates and parabens, noting that these ingredients can be irritating and drying to the hair and scalp. If a child has sensitive skin or allergies, Saleem opts for hypoallergenic products.
We also need to ensure that less toxic alternatives are available and accessible to all consumers. It’s often under-resourced, low-income populations who suffer the burden of environmental exposures and do not have access or cannot afford these safer alternatives. -- Lesliam Quirós-Alcalá.
Lesliam Quirós-Alcalá, an assistant professor in the department of environmental health and engineering at the Johns Hopkins Bloomberg School of Public Health, said current regulatory loopholes on product labeling still allow manufacturers to advertise their cosmetics and personal care products as “gentle” and “natural.” However, she said, those terms may be misleading as they don’t necessarily mean the contents are less toxic or harmful to consumers.
“We also need to ensure that less toxic alternatives are available and accessible to all consumers,” Quirós-Alcalá said, “as often alternatives considered to be less toxic come with a hefty price tag.” As a result, “it’s often under-resourced, low-income populations who suffer the burden of environmental exposures and do not have access or cannot afford these safer alternatives.”
To advocate for safer alternatives, Quirós-Alcalá suggests that parents turn to consumer groups involved in publicizing the harms of personal care products. The Campaign for Safe Cosmetics is a program of Breast Cancer Prevention Partners, a national science-based advocacy organization aiming to prevent the disease by eliminating related environmental exposures. Other resources that inform users about unsafe ingredients include the mobile apps Clearya and Think Dirty.
“Children are not little adults, so it’s important to increase parent and consumer awareness to minimize their exposures to toxic chemicals in everyday products,” Quirós-Alcalá said. “Becoming smarter, more knowledgeable consumers is the first step to protecting your family from potentially harmful and toxic ingredients in consumer products.”