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Berkeley startup wins government award to develop radiation and lead poisoning treatment

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Berkeley startup wins government award to develop radiation and lead poisoning treatment

Whether its lead from old buildings, arsenic from contaminated food or strontium fallout from a nuclear explosion, heavy metals that enter the body pose a serious health threat.

With chemical properties exceedingly similar to typical nutrients like iron and calcium, toxic metals look virtually the same to the body. So, it starts incorporating the toxic elements into the skeleton, liver and brain.

Saving a patient requires removing the sparse toxic metals from the body with more than surgical precision, while leaving the abundant life-sustaining nutrients intact.

For many toxic elements, doctors have few options.

Now, a startup spun out of UC Berkeley and the Department of Energy’s Lawrence Berkeley National Laboratory hopes to change that.

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Recently, HOPO Therapeutics won a nearly $10-million initial contract from the Biomedical Advanced Research and Development Authority of the U.S. Department of Health and Human Services. The research authority is tasked with developing defenses against major public health threats, such as a pandemic or a chemical weapons attack.

“This is a priority for [the authority] — the development of new products that can be used to address these types of threats,” said Julian Rees, chief executive of HOPO Therapeutics, who started working on the drug at Berkeley Lab. “So, it’s been really exciting for us to partner with BARDA.”

Since BARDA was created by Congress in 2006, it’s supported 61 drugs through the Food and Drug Administration’s approval process. The authority also played an essential role in Operation Warp Speed to develop the COVID-19 vaccine.

HOPO Therapeutics’ drugs are designed to chemically bond with toxic metals only. By bonding, the medicine transforms the reactive metals into benign molecules that have little interest in interacting with different compounds in the body. The body can then easily excrete the metals.

Currently, few of these types of drugs — called chelators, derived from the Greek word for claw — are approved by the FDA. Those select few that have been approved have a hard time distinguishing between toxic metals and essential nutrients.

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“HOPO chelators are extremely promising in that regard,” said Justin Wilson, a biochemistry professor at UC Santa Barbara who studies chelators and was not involved in HOPO Therapeutics work. “What the data show is that they have a very high selectivity for radioactive elements” over essential metals like zinc and calcium.

The HOPO chelators could potentially fill a crucial gap in lead poisoning treatment.

While the Centers for Disease Control and Prevention says a concentration of 3.5 micrograms of lead for every deciliter of blood constitutes lead poisoning, it doesn’t recommend treatment to remove lead until the concentration reaches over 45 micrograms, because of the adverse effects of existing treatments.

“So, there’s this huge window of people — primarily children — who have lead poisoning, but there’s no treatment available,” Rees said.

Lead poisoning can result in brain function impairment, fatigue, weight loss, paralysis and even death. It disproportionately affects children, whose bodies seek extra calcium — which lead can be mistaken as — to build bones.

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Current chelators designed to treat lead poisoning can also remove essential metals such as calcium and zinc. If the concentration of lead is too low, the drugs would remove too much natural metal before putting a sizable dent in the amount of lead in the body.

Treating radiation poisoning is harder. Lead is a single element, but there’s a whole suite of elements with radioactive forms.

For radioactive elements, “there’s no real common denominator. … They belong to all different kinds of chemical families,” said Ira Helfand, past president of the International Physicians for the Prevention of Nuclear War.

“People who are exposed to these … are in big trouble and are liable to radiation sickness, liable to cancer down the road if they survive post-exposure.”

In a complex and messy real-world nuclear or radioactive disaster, Helfand said, HOPO’s medicine could serve only as a small part of the armor against radiation.

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Much of the harm inflicted on victims of a nuclear strike — or nuclear plant catastrophe — comes from high-velocity radiation particles that pierce the body, damaging cells and their DNA. Only a small fraction of the injuries come from heavy metals that emit radiation from within the body.

And even then, some of the most abundant radioactive metals in nuclear fallout are particularly good at mimicking nutrients in the body, making it too difficult for the HOPO chelators to isolate them.

Instead, HOPO’s drug, which can target uranium and plutonium — elements found in nuclear weapons before they detonate — is better equipped to protect bomb makers, nuclear plant operators and victims of “dirty bombs,” conventional explosions that scatter radioactive material to harm bystanders.

Although state-of-the-art chelators approved by the FDA often need to be injected via an IV, HOPO drugs could be taken orally.

“If you think about the setting in which you want to apply this — where would you be getting exposed to radioactive elements? Typically some emergency situation,” Wilson said. “Having something on the field where you can take this as a pill very rapidly I think is a really big advantage.”

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HOPO Therapeutics said the initial contract could be extended to more than $226 million, should development go well. The next steps for the company include demonstrating that the drug could be easily manufactured in large quantities — not just small samples for the lab — and human trials to study potential negative side effects.

The company’s ultimate goal is FDA approval.

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In 'concerning development,' officials say H5N1 bird flu has infected a pig in Oregon

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In 'concerning development,' officials say H5N1 bird flu has infected a pig in Oregon

Oregon state and federal officials confirmed Wednesday that H5N1 bird flu was found in a pig living Crook County — the first such swine infection reported in the current outbreak.

The strain of bird flu virus in the pig is slightly different than the one that has been plaguing dairy cows in California and other states, which is known as B3.13. Instead, it is called D1 and originates from wild birds that likely came along the migratory Pacific flyway.

Both strains are H5N1; they just followed slightly different evolutionary trajectories, which is reflected in their genetic sequence.

Finding the flu virus in a pig, regardless of the strain, is a concerning development, say scientists.

“This is one big event that everyone has feared,” Rick Bright, a virologist and the former head of the U.S. Biomedical Advanced Research and Development Authority.

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Swine are considered by health officials to be efficient influenza mixing bowls: They are susceptible to both avian and human flu viruses and can potentially provide an opportunity for different viruses to exchange genetic materials and become a greater threat to humans.

“Experts and commentators have minimized the outbreak to date, saying, ‘but it’s not in pigs yet.’ Well, now it seems to be, and just in time for the other critical ingredient to brew a pandemic virus … seasonal human flu viruses,” Bright said.

He said it’s critical that federal authorities move quickly and transparently.

“We cannot afford to keep playing a wait and see game,” he said. “We all know how quickly this virus can emerge and spread. We must immediately remove it from these farms, increase all surveillance, and begin planning actions for a larger response. … We cannot afford to do wait and see … again. We need to act now.”

John Korslund, a retired U.S. Department of Agriculture veterinarian epidemiologist, was a bit more circumspect.

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According to officials, the infected pig was one of five living on small farm. All pigs were tested and euthanized. Results for two of the other pigs were negative, while the others are pending. In addition, federal authorities say only “low viral levels” were detected in the samples.   

Korslund said this suggests the virus may require close contact, such as shared water, to move.

“I’ll be more concerned if it travels by aerosol to a confinement building,” he said, adding that a pig serving as mixing vessel is “not as likely in backyard herds — a bigger risk in commercial herds where flu is more endemic.”

The Oregon farm, which is located in an area just east of Bend, is not a commercial operation, according to the U.S. Department of Agriculture. It’s animals were not destined for commercial food production.

As a result, federal officials say there is no concern about the safety of the nation’s pork supply. They also note that cooking foods properly and pasteurizing dairy products inactivates the virus.

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The farm where the pigs were living is the same one where 70 infected “backyard birds” were tested and euthanized last week after H5N1 was detected. The farm is under quarantine and the state’s department of agriculture is surveilling the area.

Those birds had the D1 version, which suggests they were not infected by dairy cows. Instead, it is likely they got it from wild birds.

“Based on recent diagnostic results, it’s apparent that migratory waterfowl are moving this new ‘D’ genotype down the Pacific Flyway,” said Bryan Richards, the Emerging Disease Coordinator at the U.S. Geological Survey’s National Wildlife Health Center.

In the past two weeks, there have been several outbreaks in commercial and backyard flocks in British Columbia, Washington and Oregon. California’s state veterinarian, Rebecca Jones, told The Times on Tuesday that a small backyard flock in Santa Rosa was also infected by the D1 strain.

That flock is not listed on the USDA’s website.

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In addition, two commercial chicken farms in California’s Kings County, and a backyard flock in Tulare County, were reported infected on Tuesday. Again, the particular strains of H5N1 in those birds has not been identified.

Scientists are frustrated that genetic sequencing has not been forthcoming on some of these latest outbreaks.

“The big deal for me,” about the pig, said Korslund, is the “unwillingness to name the clade. Was it the dairy clade or something else? We also have another poultry outbreak in Oregon with dairy herds around that no one has owned up to [regarding] the sub-clade. If it is B3.13, they need to test dairy herds.”

A 2017 information sheet on agriculture in Crook County noted there were 47,399 cows and calves in the county.

According to the USDA, there have been 393 herds infected with H5N1 since March across 14 states — not including Oregon. Almost half of those — 193 — are in California.

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Asked if a new strain of H5N1 in the mix was going to complicate the situation, Maurice Pitesky, an associate professor with a research focus on poultry health and food-safety epidemiology at UC Davis, said yes.

“This is year three of migration, where the virus seems to be coming back down” via birds who summered in the Arctic and swapped viruses, he said. “If that keeps happening, it makes it much more challenging to stop.”

He said that a few years ago, he worked on a computer model that could predict where the virus would show up as birds migrated south. He said it worked, and now people are asking him to develop another.

“I can’t,” he said. “It’s too complex now. Now it’s in urban wastewater, it’s in wild mammals. It’s in dairy cows. It’s in song birds. It’s in waterfowl and shore birds. It’s in marine mammals … We’ve never had anything like this before at a species level, at a geographical level, and at a food security level. Wow.”

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As Musk seeks to launch tens of thousands of Starlink satellites, space researchers urge caution

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As Musk seeks to launch tens of thousands of Starlink satellites, space researchers urge caution

Over 100 space researchers signed a letter urging the federal government to perform an environmental review before allowing SpaceX to continue launching thousands of satellites for its internet service, Starlink.

The Federal Communications Commission has licensed Elon Musk’s company to launch nearly 12,000 satellites into space — more than double the number of non-SpaceX satellites orbiting Earth. SpaceX is asking the FCC to allow it to launch over 20,000 more.

While the FCC evaluates the potential harms of satellite constellations, it currently exempts almost all telecommunications projects — including satellites — from facing formal environmental reviews. The researchers’ letter, released on Thursday, argues that much has changed since the rule was created almost four decades ago.

“This is a new technology,” said Lucas Gutterman, the director of the Designed to Last Campaign at Public Interest Research Groups (PIRG), which organized the letter. “It could have benefits for the public and that’s great, but the benefits need to be weighed against the potential harms, and the way you do that is with an environmental review.”

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Gutterman said PIRG has heard back from the FCC and is excited to meet with the agency to discuss the group’s concerns.

The Starlink constellation provides internet coverage across the globe, especially to rural communities and countries without reliable cell tower service. The service has provided internet access to Ukrainian soldiers, hurricane victims and commercial flight passengers.

SpaceX’s satellites are designed to have a roughly five-year lifespan, after which SpaceX ground controllers will deorbit the satellites, let them burn up in Earth’s atmosphere and launch replacements. This injection of metals and other compounds into the upper atmosphere from the incineration of the spent satellites has the potential to disturb the delicate balance of elements and molecules in the air, the letter argues.

“The industry has moved faster than regulators can act and faster than the public has really been aware,” Gutterman said. “The results aren’t in — we just don’t actually have the data on what effects this new technology could have.”

In a 2022 report, the Government Accountability Office — a nonpartisan federal agency tasked with saving taxpayer money and increasing government efficiency — recommended the FCC review whether the satellite constellations normally have significant environmental impacts. The FCC agreed with the findings.

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The space researchers who signed the letter not only study the effects of satellites and rocket launches on the atmosphere, but also rely on clear skies for their observations.

As satellites whiz past the field of view of telescopes, they leave streaks in the astronomers’ images. To compensate, scientists have had to frequently retake images and develop more sophisticated computer programs to remove the streaks.

“Picture an open book. Then picture a big marker streak across the page,” said David Jewitt, a distinguished professor of astronomy at UCLA who signed the letter. “That’s what they do.”

Jewitt first heard about the letter while dealing with satellite streaks on his observations from a telescope in Spain.

“It was so obvious that the number of satellite trails is just way way up since I started doing astronomy,” he said. “People want to use space for good purposes. Communication is a good purpose. … So, there has to be some moderation between the effective use of space and its effects on our view of the night sky.”

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Environmental review of satellite mega-constellations would be a first step along a path of much-needed space policy reform, said Gutterman.

Currently there is limited international cooperation in regulation of satellite constellations, and within the United States, oversight of different aspects of their life cycles — from launch to orbit to decommissioning — is handled by separate agencies.

Setting clear international standards and streamlining the process in the U.S. would be a win-win for concerned scientists and the space industry, said Gutterman.

It’s not the first time Starlink has run into pushback from the public and government officials. After the first few batches of satellites were launched in 2019, astronomers around the world raised concerns about the satellites’ reflectivity. In response, SpaceX began applying a coating to the satellites to make them less shiny.

And earlier this month, the California Coastal Commission rejected a SpaceX plan to increase the number of rocket launches from Vandenburg Space Force Base to 50 a year, on the grounds that SpaceX was increasingly using the launches for their Starlink satellites instead of for military missions.

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SpaceX subsequently sued.

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Opinion: I'm a doctor in East L.A. and Beverly Hills. I want to treat obesity the same way in both places

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Opinion: I'm a doctor in East L.A. and Beverly Hills. I want to treat obesity the same way in both places

As a diabetes specialist, I’ve treated thousands of patients, some in Beverly Hills and some in East Los Angeles. My Beverly Hills patients live to become healthy 80- and 90-year-olds. I can’t remember when my last patient from this community lost their vision, had an amputation or started dialysis. Almost none have heart attacks or strokes.

But in under-resourced parts of East L.A. I see people every week in their 40s and 50s who have developed life-altering, preventable diabetes complications — blindness, kidney failure, the loss of a limb. These patients rarely live to grow old.

Obesity is one of the drivers of this heartbreaking disparity. Health-conscious Beverly Hills is replete with doctors’ offices, fresh food and gyms. Most residents there can spend what they need to maintain a healthy diet and get help to control diabetes. In East Los Angeles, where for some a home refrigerator can be a luxury, diabetes and obesity afflict thousands of families who depend on fast and processed food to provide the affordable calories they need to survive.

The tale of these two neighborhoods is replicated across the country. Obesity kills 300,000 Americans annually. It is associated with increased risk of more than 200 other diseases, including heart disease, diabetes, cancer and dementia. According to modeling by my colleagues at the USC Schaeffer Institute for Public Policy & Government Service, the average American will soon have obesity. Black and Latino individuals experience higher rates of severe obesity compared to non-Latino white people, translating into higher rates of chronic diseases.

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Despite decades of public health efforts, obesity increases. Some recent lifestyle interventions have shown promise; for the most part, however, simply urging people in minority neighborhoods to change their diets has proved ineffective. Although providing resources and education do help, these initiatives are often grant-funded and not routinely available. Lots of proposed solutions that might resonate in wealthier communities, such as recommending “fixed” foods, with reduced sugar, fats and preservatives, just don’t fly in East L.A. Cost and availability of healthy foods are two reasons. So is culture. Where there is food insecurity, familiar food can be a celebration not easily surrendered.

But at least one weight-loss remedy that is enormously popular in Beverly Hills also works across town: medication. New drugs such as Wegovy/Ozempic (semaglutide) and Zepbound/Mounjaro (tirzepatide), if used with proper medical supervision, can often reduce body weight by 15% or more. Several of my patients with severe obesity have lost close to 100 pounds and avoided much more burdensome metabolic surgery.

The drugs come with list prices that can top $1,200 a month, although health insurance companies often negotiate deep discounts. So far Medicare is not helping reduce patient costs because it is barred from paying for weight-loss drugs. But Medicaid, the state/federal program that covers the poor, faces no such constraint. And it has a big price advantage: By law, it automatically gets the biggest discounts negotiated by any payer.

Several states, including California, have added one or more of the obesity drugs to their Medicaid formularies. In Los Angeles County, use is still not widespread as doctors have to secure prior authorizations through Medicaid managed-care organizations and teach patients how to inject themselves at home. But among those patients who are taking the drugs, we are seeing improvements in health.

The balance between the drugs’ prices and their benefits is a fraught debate, mostly centered on what would happen to public and private sector budgets under broadened coverage. The Congressional Budget Office recently concluded that the costs of authorizing coverage in Medicare would exceed the benefits of beneficiaries’ improved health for the next 10 years.

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I’m not an economist, but I know that focusing just on government ledgers can be shortsighted. I see firsthand that medications have a big role to play in the treatment of obesity and diabetes. Like many other drugs I have prescribed for other diseases, over time they will become more affordable while reducing the costs of treating associated illnesses. Research at USC Schaeffer projects that Medicare coverage of obesity treatments could generate $4 trillion in social value to Americans over three decades.

Of course we also need to keep pressing for better, broader fresh food access, healthier diets and safe places to exercise around the clinic where I work in East L.A. However, use of these newer medications in any part of town can provide true benefit even if lifestyle changes are harder to implement.

I’m in favor of whatever works for my patients, no matter where they live, as long as preventive healthcare and individualized treatment plans are part of the equation.

In addition to her medical practice, Anne L. Peters is a senior scholar at the USC Schaeffer Institute for Public Policy & Government Service.

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