THE BODY ELECTRIC I enjoyed reading “Shock and Awe,” Kenneth C. Catania’s article on the electric eel. I’m curious about what was done to determine how the eel is protected from shocking itself. My guess is that the nervous system is somehow insulated or shielded. BRUCE ROGERS Via e-mail CATANIA REPLIES: Rogers is in good company: lots of people are curious about why these eels don’t shock themselves—including me. No one seems to know the details, but I think Rogers is on the right track. It seems inevitable there are paths of very low resistance, along with areas of electrical insulation, within the animals (we do know the latter exists around their electrocytes—the biological batteries). But I can say this much: the eels are just barely protecting themselves. Sometimes an eel that has curled itself to amplify the electrical effect on its prey ends up activating its own fins with each high-voltage volley. So the experience is at least mildly shocking, even to the eel. HISTORY OF HIV TREATMENT In “Outsmarting a Virus with Math,” Steven Strogatz writes about the mathematics of HIV replication in humans (excerpted from his book Infinite Powers). He rightly praises immunologist Alan Perelson’s calculus skills in dissecting clinical data from antiviral drug trials. But Martin Nowak and Sebastian Bonhoeffer, both then at the University of Oxford, working with virologist George Shaw and others, published analyses and conclusions in the same 1995 issue of Nature that were essentially identical to those in the report by Perelson and his colleague David Ho. Their contributions should not be overlooked. Strogatz’s statement that calculus “led to triple-combination therapy [for HIV]” also does not truly reflect the events of the time. The various mathematical calculations did not drive the development of multidrug combination therapy, although they did eventually guide how the drugs might best be used. The key factor in effectively suppressing HIV replication in vivo was the clinical development of protease inhibitors in the decade preceding the two 1995 papers. The complex series of events that took place in the early 1990s, along with the contributions made by many people, have been thoroughly summarized in review articles. Yet contemporaneous coverage by the media has skewed public perceptions of what happened in the critical period when HIV infection transitioned from being almost always fatal to becoming a manageable, chronic disease. Strogatz’s article reinforces the oversimplification of these important historical events. JOHN P. MOORE Weill Cornell Medicine and a member of Scientific American’s Board of Advisers MASON-DIXON GRAVITAS “Quantum Gravity in the Lab,” by Tim Folger, mentions the late 18th-century experiment in which British scientist Henry Cavendish measured the mass of the earth. Inspiration for that experiment came from Charles Mason and Jeremiah Dixon’s work to settle the boundary between Pennsylvania and Maryland. Cavendish found that the plumb bobs they were using for the survey were affected by the Allegheny Mountains. MARK ARNOLD via e-mail Folger states that one of the significant problems in doing quantum gravity experiments is “the need for large superpositions that last for seconds at a time and stay close enough together so that gravity can entangle them.” Achieving that scenario, such as with one proposed experiment involving micron-wide diamond spheres, is difficult in a laboratory because the earth’s gravity is enormous as compared with micron-sized objects. And if you let objects fall in a vacuum, as in the proposed diamond sphere experiment, the required length of the shaft grows as the square of the duration. It seems like such experiments could be carried out in an almost zero-g environment such as the International Space Station or even in a small test satellite. Then the duration could easily run to a day or more, and the experiment could be done multiple times. ROBERT H. BEEMAN Coral Springs, Fla. Why does gravity have to exist at the quantum level? BILL YANCEY St. Augustine, Fla. FOLGER REPLIES: I had considered opening my article with an anecdote similar to Arnold’s: In the early 1770s British scientist Nevil Maskelyne trekked to Schiehallion, a mountain in Scotland. Maskelyne wanted to see if the mountain’s mass would deflect a plum bob and then use the result to estimate the earth’s density. The result, as calculated from Maskelyne’s data by mathematician Charles Hutton, was less than 20 percent off today’s accepted value. Maskelyne’s work shows how ingenious Cavendish was: he didn’t need to use a mountain as a test mass—only the heavy spheres in his shed. Regarding Beeman’s suggestion: Physicists have proposed a space mission to test quantum superpositions, called MAQRO. But it hasn’t been funded yet. In answer to Yancey: If gravity doesn’t exist at the quantum level, then why does it exist at our level? Where gravity comes from—what its fundamental nature is—is what physicists are trying to find out. TALKING ABOUT REGENERATION In “A Shot at Regeneration,” Kevin Strange and Viravuth Yin discuss the compound MSI-1436, which removes limits to the body’s ability to regenerate cells by blocking the enzyme protein tyrosine phosphatase 1B (PTP1B). The article speaks of research being directed toward muscular dystrophy. I am wondering if application research on MSI-1436 would be appropriate for arthritis or crippling spinal cord injuries. CHRIS SCHOFIELD via e-mail STRANGE REPLIES: PTP1B is expressed in virtually all tissue and cell types, where it functions to inhibit receptor tyrosine kinase (RTK) signaling. RTKs activate multiple cellular processes that must work together in a coordinated manner for regeneration to occur. By inhibiting PTP1B, MSI-1436 thus enhances the activity of diverse, RTK-regulated cellular pathways required for tissue regeneration. Given this arrangement, we suspect MSI-1436 may have various disease indications whereby stimulating tissue repair and regeneration would be therapeutically valuable. But a great deal of very careful science must be carried out before we know for certain. Our work to date has been focused on heart and skeletal muscle injury. BIPARTISAN CLIMATE ACTION “Feverish Planet,” by Tanya Lewis [Advances, March 2019], covers the direct health effects of global warming. Remedies are only briefly touched on: phasing out coal and carbon-based fuels in vehicles. But how do we do this? For the U.S., there is a simple answer: pass the Energy Innovation and Carbon Dividend Act, which is already in the House of Representatives, with bipartisan support. The act taxes carbon emissions and returns the funds to every U.S. resident. Climate scientists and economists have endorsed this concept. And the “cash back” will appeal to voters and therefore to members of Congress. CHARLES M. BAGLEY, JR. Seattle

I enjoyed reading “Shock and Awe,” Kenneth C. Catania’s article on the electric eel. I’m curious about what was done to determine how the eel is protected from shocking itself. My guess is that the nervous system is somehow insulated or shielded.

BRUCE ROGERS Via e-mail

CATANIA REPLIES: Rogers is in good company: lots of people are curious about why these eels don’t shock themselves—including me. No one seems to know the details, but I think Rogers is on the right track. It seems inevitable there are paths of very low resistance, along with areas of electrical insulation, within the animals (we do know the latter exists around their electrocytes—the biological batteries). But I can say this much: the eels are just barely protecting themselves. Sometimes an eel that has curled itself to amplify the electrical effect on its prey ends up activating its own fins with each high-voltage volley. So the experience is at least mildly shocking, even to the eel.

HISTORY OF HIV TREATMENT

In “Outsmarting a Virus with Math,” Steven Strogatz writes about the mathematics of HIV replication in humans (excerpted from his book Infinite Powers). He rightly praises immunologist Alan Perelson’s calculus skills in dissecting clinical data from antiviral drug trials. But Martin Nowak and Sebastian Bonhoeffer, both then at the University of Oxford, working with virologist George Shaw and others, published analyses and conclusions in the same 1995 issue of Nature that were essentially identical to those in the report by Perelson and his colleague David Ho. Their contributions should not be overlooked.

Strogatz’s statement that calculus “led to triple-combination therapy [for HIV]” also does not truly reflect the events of the time. The various mathematical calculations did not drive the development of multidrug combination therapy, although they did eventually guide how the drugs might best be used. The key factor in effectively suppressing HIV replication in vivo was the clinical development of protease inhibitors in the decade preceding the two 1995 papers.

The complex series of events that took place in the early 1990s, along with the contributions made by many people, have been thoroughly summarized in review articles. Yet contemporaneous coverage by the media has skewed public perceptions of what happened in the critical period when HIV infection transitioned from being almost always fatal to becoming a manageable, chronic disease. Strogatz’s article reinforces the oversimplification of these important historical events.

JOHN P. MOORE Weill Cornell Medicine and a member of Scientific American’s Board of Advisers

MASON-DIXON GRAVITAS

“Quantum Gravity in the Lab,” by Tim Folger, mentions the late 18th-century experiment in which British scientist Henry Cavendish measured the mass of the earth.

Inspiration for that experiment came from Charles Mason and Jeremiah Dixon’s work to settle the boundary between Pennsylvania and Maryland. Cavendish found that the plumb bobs they were using for the survey were affected by the Allegheny Mountains.

MARK ARNOLD via e-mail

Folger states that one of the significant problems in doing quantum gravity experiments is “the need for large superpositions that last for seconds at a time and stay close enough together so that gravity can entangle them.” Achieving that scenario, such as with one proposed experiment involving micron-wide diamond spheres, is difficult in a laboratory because the earth’s gravity is enormous as compared with micron-sized objects. And if you let objects fall in a vacuum, as in the proposed diamond sphere experiment, the required length of the shaft grows as the square of the duration.

It seems like such experiments could be carried out in an almost zero-g environment such as the International Space Station or even in a small test satellite. Then the duration could easily run to a day or more, and the experiment could be done multiple times.

ROBERT H. BEEMAN Coral Springs, Fla.

Why does gravity have to exist at the quantum level?

BILL YANCEY St. Augustine, Fla.

FOLGER REPLIES: I had considered opening my article with an anecdote similar to Arnold’s: In the early 1770s British scientist Nevil Maskelyne trekked to Schiehallion, a mountain in Scotland. Maskelyne wanted to see if the mountain’s mass would deflect a plum bob and then use the result to estimate the earth’s density. The result, as calculated from Maskelyne’s data by mathematician Charles Hutton, was less than 20 percent off today’s accepted value. Maskelyne’s work shows how ingenious Cavendish was: he didn’t need to use a mountain as a test mass—only the heavy spheres in his shed.

Regarding Beeman’s suggestion: Physicists have proposed a space mission to test quantum superpositions, called MAQRO. But it hasn’t been funded yet.

In answer to Yancey: If gravity doesn’t exist at the quantum level, then why does it exist at our level? Where gravity comes from—what its fundamental nature is—is what physicists are trying to find out.

TALKING ABOUT REGENERATION

In “A Shot at Regeneration,” Kevin Strange and Viravuth Yin discuss the compound MSI-1436, which removes limits to the body’s ability to regenerate cells by blocking the enzyme protein tyrosine phosphatase 1B (PTP1B). The article speaks of research being directed toward muscular dystrophy. I am wondering if application research on MSI-1436 would be appropriate for arthritis or crippling spinal cord injuries.

CHRIS SCHOFIELD via e-mail

STRANGE REPLIES: PTP1B is expressed in virtually all tissue and cell types, where it functions to inhibit receptor tyrosine kinase (RTK) signaling. RTKs activate multiple cellular processes that must work together in a coordinated manner for regeneration to occur. By inhibiting PTP1B, MSI-1436 thus enhances the activity of diverse, RTK-regulated cellular pathways required for tissue regeneration. Given this arrangement, we suspect MSI-1436 may have various disease indications whereby stimulating tissue repair and regeneration would be therapeutically valuable. But a great deal of very careful science must be carried out before we know for certain. Our work to date has been focused on heart and skeletal muscle injury.

BIPARTISAN CLIMATE ACTION

“Feverish Planet,” by Tanya Lewis [Advances, March 2019], covers the direct health effects of global warming. Remedies are only briefly touched on: phasing out coal and carbon-based fuels in vehicles. But how do we do this?

For the U.S., there is a simple answer: pass the Energy Innovation and Carbon Dividend Act, which is already in the House of Representatives, with bipartisan support. The act taxes carbon emissions and returns the funds to every U.S. resident. Climate scientists and economists have endorsed this concept. And the “cash back” will appeal to voters and therefore to members of Congress.

CHARLES M. BAGLEY, JR. Seattle