Article by Lalita Panicker, Consulting Editor, Views and Editor, Insight, Hindustan Times, New Delhi
Public health advocates are applauding the news that President Joe Biden intends to name Mandy Cohen, a physician and public health expert with broad government experience, to lead the U.S. Centres for Disease Control and Prevention (CDC).
Biden will appoint Cohen by the end of the month to replace current CDC Director Rochelle Walensky when she steps down, The Washington Post reported on 1 June. The White House did not respond to requests for comment and Cohen could not be reached.
Cohen, age 44, is an internist with an M.D. from Yale University and a master’s in public health from Harvard University. She held increasingly high-level posts at the U.S. Centres for Medicare and Medicaid Services during former President Barack Obama’s administration.
As North Carolina’s secretary of health and human services from 2017 until 2022, Cohen won praise for steering the state’s pandemic response with a transparent, bipartisan approach. She is now at Aledade, a company that works with primary health care practices.
Cohen is “savvy, courageous, passionate, and inspiring,” says Nancy Messonnier, former head of CDC’s respiratory diseases centre who is now dean at the University of North Carolina’s school of public health. In Washington, D.C., and North Carolina, “people really
thought a lot of her,” adds Georges Benjamin, executive director of the American Public Health Association.
A $9.2 billion, 13,000-employee agency, CDC faced the music during the pandemic on everything from its rollout of COVID-19 tests to public communications. Walensky, an infectious disease physician who came to CDC from academia, launched an overhaul in August 2022 to improve communications and speed CDC’s scientific publications. It’s not clear whether Cohen, if appointed, would continue with those changes.
The CDC directorship does not currently require Senate confirmation. But the appointment is certain to be scrutinized by lawmakers from both parties.
Some 11% of Indians are diabetic, a government study found, adding that diabetes, hypertension and obesity are much more common in India than previously estimated. www.reuters.com/world/india/india-study-estimates-11-population-is-diabetic-2023-06-09/#:~:text=ICMR%2C%20which%20funded%20the%20study,by%20the%20International%20Diabetes%20Federation.
The study of more than 113,000 people also found that around 15% of Indians were pre-diabetic and around 35% have hypertension. It was conducted between October 2008 and December 2020 across 31 Indian states and territories.
“It is quite evident from the study results that India has a substantial population at risk of cardiovascular disease and other long-term organ
complications,” R.S. Dhaliwal, head of the non-communicable diseases division at the Indian Council of Medical Research (ICMR), said in a statement.
India is often referred to as the ‘Diabetes Capital of the World’, as it accounts for 17 percent of the total number of diabetics in the world. There are currently close to 80 million people with diabetes in India and this number is expected to increase to 135 million by 2045.
The Indian government says unhealthy diets, lack of physical activity as well as the harmful use of alcohol and tobacco are factors behind the rise in cases of diabetes.
India’s health secretary said last month that the “lifestyle of a large section of the population has become more sedentary than before” and that the burden of metabolic diseases was growing.
The U.S. National Clinical Care Commission has also estimated that about 11% of the U.S. population has diabetes.
Generations of medical and biology students have been instilled with a dim view of bilirubin. Spawned when the body trashes old red blood cells, the molecule is harmful refuse and a sign of illness. High blood levels cause jaundice, which turns the eyes and skin yellow and can signal liver trouble. New-borns can’t process the compound, and although high levels normally subside, a persistent surplus can cause brain damage.
Yet later this year up to 40 healthy Australian volunteers may begin receiving infusions of the supposedly good-for-nothing molecule. They will be participating in a phase 1 safety trial, sponsored by the South Korean company Bilix, that could pave the way for testing bilirubin as a treatment in organ transplant recipients and patients with conditions such as multiple sclerosis and stroke. www.science.org/content/article/can-toxic-bilirubin-treat-variety-illnesses
The company’s ambitions reflect a new view of bilirubin that emerged as researchers amassed lab, animal, and epidemiological data suggesting it plays a vital role in the body as a fierce antioxidant and anti-inflammatory.
“There’s lots of levels of evidence that it’s more than just a metabolic waste product,” says molecular epidemiologist Laura Horsfall of University College London.
Bilirubin naturally arises when the spleen and other parts of the body dispose of heme, the core of the haemoglobin molecule in red blood cells. Heme is highly toxic; bilirubin, the breakdown product in mammals, is less so. Each week the average person generates about 2 grams of the yellowish substance, most of which the liver dumps into the intestines for elimination from the body.
There have been hints that bilirubin plays physiological roles. When birds and reptiles break down heme, Horsfall says, they produce a different molecule that is non-toxic and soluble in body fluids. That mammals opt for bilirubin even though it is toxic and insoluble suggests it may offer some benefits.
One may be its power to neutralize reactive oxygen species (ROS), destructive by-products of metabolism that can injure DNA and other important cellular molecules. When mixed with lab-grown cells, bilirubin shields them from ROS, and mice lacking the molecule are more vulnerable to oxidative damage.
About 10% of humans carry gene variants that result in slightly high bilirubin levels. For instance, people with a condition known as Gilbert syndrome don’t make enough of a protein that helps prepare bilirubin for excretion. As a result, their blood concentrations of the molecule can be more than twice the upper limit of normal. But they don’t have jaundice or any serious symptoms.
More striking, multiple studies suggest people who have moderately elevated bilirubin levels—whether because of Gilbert syndrome or other causes—are less likely to develop a plethora of illnesses, including heart disease, inflammatory bowel disease, diabetes, and many types of cancer. On the flip side, people with relatively low bilirubin levels are more vulnerable to these diseases.
More evidence comes from Mendelian randomization studies, which compare the health of people who carry different gene variants to tease out cause and effect. In 2020, Horsfall and her colleagues analysed data on more than 377,000 people from the UK Biobank, a national health registry. They discovered that people with two copies of a gene version that leads to higher bilirubin levels had a 17% lower risk of developing lung cancer, and the effect was even larger in smokers. Reactive oxygen molecules flood the lungs, and the extra bilirubin may help counteract their effects, Horsfall says.
Suggestions that the molecule has a positive side have encouraged researchers to try to boost its levels in the past. One of the first was physician Philip Hench of the Mayo Clinic, who in the 1930s noticed
that his rheumatoid arthritis (RA) patients improved when they developed jaundice. He tried to replicate the effect in several ways, including by injecting patients with bilirubin mixed with another molecule, but the results were inconsistent. (Hench later shared a Nobel Prize for identifying cortisone and treating RA with it.)
Such early efforts to turn bilirubin into a therapy faltered because of its balky nature. The molecule is insoluble and degraded by light, and injected doses are rapidly broken down or excreted.
Bilix’s co-founder, chemist Sangyong Jon of the Korea Advanced Institute of Science and Technology, and colleagues overcame these problems by affixing the water-soluble molecule polyethylene glycol to one end of bilirubin. As they reported in 2016, in water the hybrid molecules huddle to form nanoparticles. These tiny spheres make the bilirubin soluble, protect it from light, and extend its life span in the blood from less than 20 minutes to several hours, says Myung Kim, Bilix’s co-founder and CEO. They can also enter immune cells, allowing their bilirubin cargo to combat reactive oxygen species inside these cells and thereby fight inflammation.
A chemist at Bilix also figured out how to synthesize bilirubin, overcoming another hurdle. Slaughterhouse animals have provided most bilirubin for research, but this source contains three slightly different varieties of bilirubin and is not suitable for therapies, Kim says.
Animal studies suggest bilirubin-toting nanoparticles are effective against a range of conditions. One is graft-versus-host disease (GVHD), a serious complication of organ and bone marrow
transplants in which immune cells in the transferred tissue attack the recipient. “We are always looking for new therapies to prevent it,” says Jin Seon Im, a clinician at the University of Texas MD Anderson Cancer Center. Because bilirubin eases inflammation, she and her colleagues decided to test the nanoparticles in mice that developed GVHD after bone marrow transplants. They found that the particles reduced tissue damage and more than doubled the animals’ survival.
Bilix chose Australia for its phase 1 trial in part because the country’s ethnic composition is similar to that of the United States, which would make it easier to get permission for future U.S. trials from the Food and Drug Administration. If the nanoparticles prove safe in the trial, due to launch in November, Kim says the company wants to test whether they can prevent tissue damage in transplanted kidneys, which are inundated by reactive oxygen species after their blood circulation resumes. Other potential targets include the skin condition atopic dermatitis, asthma, multiple sclerosis, and stroke.