Oct 8, 2020

Axios Science

Welcome back to Axios Science. This week we look at pandemic medical ethics, the history of an asteroid, clues to cancer's spread and more.

Today's newsletter is 1,729 words, a 6-minute read.

1 big thing: Medical ethics in pandemic times

Illustration: Sarah Grillo/Axios

The COVID-19 pandemic is rife with scientific and medical uncertainty, including debates about the ethics of using experimental treatments, I write with Eileen Drage O'Reilly.

The big picture: As the global pandemic continues, the tension between providing the best available care for patients and performing trials to determine whether that care is effective risks complicating the medical response.

The big question: Is it unethical to withhold a possible treatment from someone who instead receives a placebo, or to continue to administer that treatment without having collected data on whether it works?

Driving the news: President Trump received an experimental monoclonal antibody cocktail via expanded access or "compassionate use," which allows someone to access a treatment outside of a clinical trial before it is approved, provided their doctor, the drug company and the FDA agree.

  • Experts say Trump's subsequent claims of the treatment being a cure risks reducing enrollment in clinical trials, flooding companies with requests for access to a limited number of doses, and creating false hope for patients.
  • And the president's treatment raised questions about fairness — would other COVID-19 patients have similar access?
  • "It’s important that we not say the president got access to a beneficial experimental intervention because we don’t know if it is beneficial or if there are adverse events associated with it," says Alex John London, director of the Center for Ethics and Policy at Carnegie Mellon University. 

He and other ethicists say the president's treatment highlights a broader question about the ethical obligation doctors have to the science needed to determine if those treatments are effective

Between the lines: Offering patients experimental COVID-19 drugs via emergency use authorizations, expanded access programs and compassionate use can slow needed clinical trials.

  • Researchers have struggled to enroll people in clinical trials in which they may receive a placebo if patients can access a drug directly.
  • One example: "There's been some hiccups with the expanded access use for convalescent plasma, because it was something that precluded people from enrolling in a randomized control trial, so it took longer and we still don't quite know how well convalescent plasma works," says Amesh Adalja, an infectious disease physician and senior scholar at the Johns Hopkins Center for Health Security.

More than 100,000 COVID-19 patients at almost 2,800 U.S. hospitals received convalescent plasma from people who survived the virus and developed antibodies to it.

  • "It's easy for people to say you enrolled 100,000 people, there should have been a trial. But a small number of those 2,800 hospitals would have been capable of doing those trials," says the Mayo Clinic's Michael Joyner, who leads the program.
  • There are now smaller trials taking place to answer questions about the effectiveness of plasma in treating the disease in different stages.
  • But if this happens again, Joyner says programs at academic medical centers should be peeled off earlier to form clinical trials run in parallel.

The gold standard for determining whether a treatment works is through randomized controlled trials in which people are randomly assigned to receive a treatment or to be in a control group.

  • In the uncertainty and urgency of a pandemic, some physicians argue randomizing people to receive a placebo goes against physicians' ethics and that it is better to do something to help patients than do nothing.
  • "That's a false dichotomy because the question is, what should we do?" says London.

From a doctor's perspective, it's important to weigh the collective value of the early drug data and the individual needs of the patient, Adalja says.

  • Alison Bateman-House, a professor of medical ethics at NYU's Grossman School of Medicine, says she understands the emotional pull on doctors to help patients whose health is quickly deteriorating, "but it is not evidence-based medicine."
"There is no ethical obligation to give anyone an unproven substance."
— Alison Bateman-House, NYU's Grossman School of Medicine

In a forthcoming paper, London argues that when medical professionals don't have the knowledge they need to treat patients, it is their responsibility "to band together and run studies to get evidence to discharge [their] very ancient medical obligation."

What to watch: How the FDA's handling of treatments during the pandemic influences other drugs and diseases once the pandemic ends.

The bottom line: "Medicine doesn't have a good handle on uncertainty, and that is a problem," says London.

2. Catch up quick on COVID-19
Expand chart
Data: The COVID Tracking Project, state health departments; Map: Andrew Witherspoon, Sara Wise/Axios

Coronavirus infections rose in 23 states and D.C. over the past week, Axios' Sam Baker writes. "Nationwide, cases were up 6%, compared to the week before. The U.S. is now averaging roughly 43,700 new infections per day."

Most hospitalized COVID-19 patients in a new study had neurological symptoms and almost one-third had altered mental function, Axios' Marisa Fernandez reports.

Eli Lilly announced its monoclonal antibody treatment is effective in treating patients with COVID-19 who have not been hospitalized and is seeking emergency use authorization from the FDA, per Matthew Herper of STAT.

The FDA posted new vaccine guidance requiring clinical trial participants to be monitored "for a median of two months after they receive their final dose," per Axios' Caitlin Owens. The White House cleared the stricter guidelines after reportedly blocking them earlier.

3. An asteroid's watery history

A global map of Bennu. Photo: Simon et al., Science (2020)

The space rock that eventually gave rise to the asteroid Bennu — currently being studied from close range by NASA's OSIRIS-REx spacecraft — may have had flowing water, according to a new study in the journal Science.

Why it matters: Asteroids are thought to be building blocks left over from the early days of the solar system, and understanding their nature could provide insights into its evolution, Axios' Miriam Kramer reports.

State of play: Bennu is thought to have formed when a huge impact broke its parent body apart at some point in the relatively early days of the solar system.

  • That parent body — which likely formed from ice and rocky material — eventually heated up.
  • "When it heated up, the ice originally incorporated was turned into liquid water," Hannah Kaplan, one of the authors of the new study, told Axios.
  • The scientists behind the new study found veins of carbonate on Bennu, suggesting water was flowing through fractures in the parent body only a few million years after the formation of the solar system.

Yes, but: This finding doesn't mean there was some kind of life on the airless body, but it does lend further proof to the idea that our solar system is rich in water and perhaps the building blocks of life.

What's next: OSIRIS-REx is about to set down on Bennu to sample the space rock this month.

  • That sample will then be sent back to Earth where scientists will be able to analyze it and learn even more about the history of the asteroid.
  • If the sample contains carbonate, for example, scientists may be able to learn even more about Bennu's possibly watery past.
  • "The diversity present in the asteroid population in terms of geology, chemistry, and geophysics is vast, and we have only scratched the surface," planetary astronomer Andy Rivkin, who wasn't affiliated with the new study, told Axios via email.

Of note: This study was one of six in a package released by Science and Science Advances this week. Read all of them here.

4. A clue about cancer's spread

Growth of normal tumor cell clusters in a mouse lung (L) compared to growth of tumor cell clusters when they are prevented from expressing epigen. Photo: Kevin Cheung/FredHutch

A signal between breast cancer cells could be a target for new drugs to block the cells from clustering, migrating and metastasizing, researchers said in early findings published in Cell last week, Eileen reports.

Why it matters: Metastatic tumors kill nearly 43,000 people from breast cancer, 33,000 from prostate cancer and 135,720 from lung cancer in the U.S. every year. Scientists are seeking ways to prevent a person's cancer from spreading to other organs and becoming more deadly.

Background: Metastatic cancer was thought to mainly originate from single cancer cells traveling to other parts of the body. But there's growing evidence that, at least in some cancers, tumors are more likely to spread throughout the body if they cluster together before traveling through a process called collective cell migration, or collective metastasis.

What they found: Using high-resolution imaging to examine clusters of breast cancer cells in mouse and human models, the team discovered a space called "nanolumina" between the cells of each cancer cluster where the cells co-opt a signaling molecule called epigen to promote the growth of clusters.

  • When epigen was suppressed within the nanolumina, primary tumor and metastatic outgrowth was greatly reduced, medical oncologist Kevin Cheung of Fred Hutchinson Cancer Research Center and his colleagues report.

What they're saying: Several scientists, who were not part of this study, said finding the nanolumina and epigen is an important early step in better understanding breast cancer metastasis that might later be found to apply to other cancers, too.

5. Worthy of your time

Axios' Nobel Prize in sciences roundup: physiology or medicine, physics, chemistry

Asbestos could be a powerful weapon against climate change (James Temple — MIT Tech Review)

Trust in science rose during the pandemic: survey (Axios)

The molecular biologist who exposed the Soviet Union (Sean B. Carroll — The Atlantic)

6. Something wondrous

A venus flytrap, Dionaea muscipula. Photo: Susannah V. Vergau/picture alliance via Getty Images

Brain-less, nerve-less Venus flytraps can store short-term memories of prey landing on their leaves in the form of concentrations of chemicals in their cells, according to a new study.

The big picture: Plants can move, some of them sometimes quite rapidly — an ability that allows plants to hunt animals. Understanding how the Venus flytrap moves opens up a way to study plants' movement mechanisms and their evolution, says Rainer Hedrich, a plant physiologist at the University of Wuerzburg.

Carnivorous Venus flytraps use tiny hairs inside each of their leaves to sense prey, triggering the leafy trap to snap shut.

  • A single, short encounter won't clamp the leaves shut, but a second one shortly thereafter will, meaning the plant can store some memory of the insect's contact with it for about 30 seconds.

How it works: Hiraku Suda of Japan's National Institute for Basic Biology and his colleagues, including Hedrich, stimulated a single sensory hair in the leaf and measured the changes in the calcium levels between cells as a result.

  • They found the first stimulation pumped up the concentration of calcium but only the second contact was enough to raise it over a threshold that closes the trap, per their study published this week in the journal Nature Plants.
  • This chemical counting of sorts is directly related to a response by the plant, Hedrich told me in an email.
  • A certain amount of calcium closes the trap, and a hormone called jasmonic acid is released along with more calcium. When those levels reach another threshold, they trigger the production of enzymes that digest prey and molecules that take up nutrients from the meal.

But unlike humans that can decide how to respond to what we memorize and count, plants cannot, he says.

  • "In other words, the flytrap is not a primitive brain. It is not what we associate with consciousness and intelligence."