How Carcinogens Cause Cancer

Siddhartha Mukherjee: So we’ve talked a little bit about the Cancer Genome. We’ve talked about the genetic changes, but I want to take one step back even before these genetic changes arise. Dr. Schwartzentruber, tell us what we know about how carcinogens cause cancer.

Doug Schwartzentruber: Well that is a challenging question because there are multiple ways for carcinogens to cause cancer and I probably should defer to some of the other panelists as well who have studied that much more than I have, but the obvious first step is how the environment which from the minute we’re born begins to interact and create feedback to say our normal cells that could then potentially be cancerous and maybe I'll stop at that point and lead into others.

Lewis Cantley: Well I can. I mean most carcinogens we think cause cancer by mutating DNA, but there are examples of carcinogens for example, forballesters [ph] which can cause skin cancers that almost certainly are to working through mutating DNA directly, although in the long run you always end up getting mutations in DNA. They are rather probably causing cells to grow at a higher rate and the higher the rate cells grow the more frequently they get mutations in DNA. Basically a cell has to go through a division cycle and make a daughter cell in order for a mutation to get locked in and that- But most really do it by directly damaging DNA, UV light, radiation directly damage the nucleotides in the DNA and many other chemical carcinogens interpolate into the DNA and at the time of cell division interfere with proper base replacement.

Harold Varmus: No, I agree entirely with this, but I would like to add two important points. First we as individuals grow up from a single cell and through many, many rounds of cell division many errors are going to occur because the ability to copy and distribute the three billion base pairs of DNA into daughter cells is an inherently error prone mechanism. We have ways to try to correct it, but nevertheless damage will occur and over the course of many cell doublings there will be damage that can be carcinogenic, so you don’t need to have external factors for cancer to arise. Cancer is probably part of our heritage. Genetic change is a good thing at the species level because we generate diversity throughout living systems.

The other point I would make is that not all carcinogens are UV light or radiation. Some of them are viruses and it’s very important to keep that in mind. It has been estimated that in developing countries for example maybe a third of cancers are caused by viruses. We actually have vaccines that are effective against some of those viruses. The human papillomavirus vaccine, the human hepatitis B virus vaccine can prevent a very large amount of cancer in those countries if the vaccines are made available, brought to patients, made affordable in poor countries. Cervical cancer is largely controlled in this country by pap smears, by early detection, and we only have about 3,000 deaths a year in this country, but in many parts of the world, India for example, and large parts of Africa, cervical cancer is the most common cause of death from cancer among women, and we now have the potential to reduce the incidence of that cancer by two-thirds using the human papillomavirus vaccine.

Seemingly every year there are new reports that something we consume or use on a daily basis is carcinogenic. But what exactly does that mean on a biological level?

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    First off, let's be clear what we mean by "hear" here. (Here, here!)

    Sound, as we know it, requires air. What our ears capture is actually oscillating waves of fluctuating air pressure. Cilia, fibers in our ears, respond to these fluctuations by firing off corresponding clusters of tones at different pitches to our brains. This is what we perceive as sound.

    All of which is to say, sound requires air, and space is notoriously void of that. So, in terms of human-perceivable sound, it's silent out there. Nonetheless, there can be cyclical events in space — such as oscillating values in streams of captured data — that can be mapped to pitches, and thus made audible.

    BepiColombo

    Image source: European Space Agency

    The European Space Agency's BepiColombo spacecraft took off from Kourou, French Guyana on October 20, 2019, on its way to Mercury. To reduce its speed for the proper trajectory to Mercury, BepiColombo executed a "gravity-assist flyby," slinging itself around the Earth before leaving home. Over the course of its 34-minute flyby, its two data recorders captured five data sets that Italy's National Institute for Astrophysics (INAF) enhanced and converted into sound waves.

    Into and out of Earth's shadow

    In April, BepiColombo began its closest approach to Earth, ranging from 256,393 kilometers (159,315 miles) to 129,488 kilometers (80,460 miles) away. The audio above starts as BepiColombo begins to sneak into the Earth's shadow facing away from the sun.

    The data was captured by BepiColombo's Italian Spring Accelerometer (ISA) instrument. Says Carmelo Magnafico of the ISA team, "When the spacecraft enters the shadow and the force of the Sun disappears, we can hear a slight vibration. The solar panels, previously flexed by the Sun, then find a new balance. Upon exiting the shadow, we can hear the effect again."

    In addition to making for some cool sounds, the phenomenon allowed the ISA team to confirm just how sensitive their instrument is. "This is an extraordinary situation," says Carmelo. "Since we started the cruise, we have only been in direct sunshine, so we did not have the possibility to check effectively whether our instrument is measuring the variations of the force of the sunlight."

    When the craft arrives at Mercury, the ISA will be tasked with studying the planets gravity.

    Magentosphere melody

    The second clip is derived from data captured by BepiColombo's MPO-MAG magnetometer, AKA MERMAG, as the craft traveled through Earth's magnetosphere, the area surrounding the planet that's determined by the its magnetic field.

    BepiColombo eventually entered the hellish mangentosheath, the region battered by cosmic plasma from the sun before the craft passed into the relatively peaceful magentopause that marks the transition between the magnetosphere and Earth's own magnetic field.

    MERMAG will map Mercury's magnetosphere, as well as the magnetic state of the planet's interior. As a secondary objective, it will assess the interaction of the solar wind, Mercury's magnetic field, and the planet, analyzing the dynamics of the magnetosphere and its interaction with Mercury.

    Recording session over, BepiColombo is now slipping through space silently with its arrival at Mercury planned for 2025.

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