HeLa, the VIP of cell lines

By  Gesa Junge, PhD

A month ago, The Immortal Life of Henrietta Lacks was released on HBO, an adaptation of Rebecca Skloot’s 2010 book of the same title. The book, and the movie, tell the story of Henrietta Lacks, the woman behind the first cell line ever generated, the famous HeLa cell line. From a biologist’s standpoint, this is a really unique thing, as we don’t usually know who is behind the cell lines we grow in the lab. Which, incidentally, is at the centre of the controversy around HeLa cells. HeLa was the first cell line ever made over 60 years ago and today a PubMed search for “HeLa” return 93274 search results.

Cell lines are an integral part to research in many fields, and these days there are probably thousands of cell lines. Usually, they are generated from patient samples which are immortalised and then can be grown in dishes, put under the microscope, frozen down, thawed and revived, have their DNA sequenced, their protein levels measured, be genetically modified, treated with drugs, and generally make biomedical research possible. As a general rule, work with cancer cell lines is an easy and cheap way to investigate biological concepts, test drugs and validate methods, mainly because cell lines are cheap compared to animal research, readily available, easy to grow, and there are few concerns around ethics and informed consent. This is because although they originate from patients, the cell lines are not considered living beings in the sense that they have feelings and lives and rights; they are for the most part considered research tools. This is an easy argument to make, as almost all cell lines are immortalised and therefore different from the original tissues patients donated, and most importantly they are anonymous, so that any data generated cannot be related back to the person.

But this is exactly what did not happen with HeLa cells. Henrietta Lack’s cells were taken without her knowledge nor consent after she was treated for cervical cancer at Johns Hopkins in 1951. At this point, nobody had managed to grow cells outside the human body, so when Henrietta Lack’s cells started to divide and grow, the researchers were excited, and yet nobody ever told her, or her family. Henrietta Lacks died of her cancer later that year, but her cells survived. For more on this, there is a great Radiolab episode that features interviews with the scientists, as well as Rebecca Skloot and Henrietta Lack’s youngest daughter Deborah Lacks Pullum.

In the 1970s, some researchers did reach out to the Lacks family, not because of ethical concerns or gratitude, but to request blood samples. This naturally led to confusion amongst family members around how Henrietta Lack’s cells could be alive, and be used in labs everywhere, even go to space, while Henrietta herself had been dead for twenty years. Nobody had told them, let alone explained the concept of cell lines to them.

The lack of consent and information are one side, but in addition to being an invaluable research tool, cell lines are also big business: The global market for cell lines development (which includes cell lines and the media they grow in, and other reagents) is worth around 3 billion dollars, and it’s growing fast. There are companies that specialise in making cell lines of certain genotypes that are sold for hundreds of dollars, and different cell types need different growth media and additives in order to grow. This adds a dimension of financial interest, and whether the family should share in the profit derived from research involving HeLa cells.

We have a lot to be grateful for to HeLa cells, and not just biomedical advances. The history of HeLa brought up a plethora of ethical issues around privacy, information, communication and consent that arguably were overdue for discussion. Innovation usually outruns ethics, but while nowadays informed consent is standard for all research involving humans, and patient data is anonymised (or at least pseudonomised and kept confidential), there were no such rules in 1951. There was also apparently no attempt to explain scientific concept and research to non-scientists.

And clearly we still have not fully grasped the issues at hand, as in 2013 researchers sequenced the HeLa cell genome – and published it. Again, without the family’s consent. The main argument in defence of publishing the HeLa genome was that the cell line was too different from the original cells to provide any information on Henrietta Lack’s living relatives. There may some truth in that; cell lines change a lot over time, but even after all these years there will still be information about Henrietta Lack’s and her family in there, and genetic information is still personal and should be kept private.

HeLa cells have gotten around to research labs around the world and even gone to space and on deep sea dives. And they are now even contaminating other cell lines (which could perhaps be interpreted as just karma). Sadly, the spotlight on Henrietta Lack’s life has sparked arguments amongst the family members around the use and distribution of profits and benefits from the book and movie, and the portrayal of Henrietta Lack’s in the story. Johns Hopkins say they have no rights to the cell line, and have not profited from them, and they have established symposiums, scholarships and awards in Henrietta Lack’s honour.

The NIH has established the HeLa Genome Data Access Working Group, which includes members of Henrietta Lack’s family. Any researcher wanting to use the HeLa cell genome in their research has to request the data from this committee, and explain their research plans, and any potential commercialisation. The data may only be used in biomedical research, not ancestry research, and no researcher is allowed to contact the Lacks family directly.

Cassini’s Sacrifice

 

By  JoEllen McBride, PhD

Our solar system is full of potential. From Earth to the frozen surface of Pluto, hydrocarbons and other complex organic molecules are surprisingly common. With every new space mission, we find the ingredients of life on more of our celestial neighbors.

 

The newest location to add to our list of places with potential for life comes from NASA’s Cassini spacecraft which began its study of Saturn in 2004. In the 13 years that Cassini has studied Saturn and its moons, it solved many mysteries and discovered some startling similarities to our own planet.

 

Saturn, at first glance, seems nothing like Earth. It is a gas giant, full of hydrogen and helium, with a possible Earth-sized core at the center. But Cassini revealed that there are phenomena occurring in the gas giant’s atmosphere that also occur on Earth. Cassini recorded video of lightning strikes on Saturn— the first taken on a planet other than our own. Since Saturn doesn’t have interference from mountains and other land features, jet streams can flow unimpeded forming a continuous hexagonal shape at the poles. But scientists are still unsure why that specific shape is created. Saturn also develops a planet-wide storm every 30 years that just happened to show up while Cassini was around in 2011– 10 years early. From the data collected by Cassini, scientists were able to determine that the storms form in a similar way to thunderstorms on Earth. Instead of adjacent hot and cold fronts mixing on Saturn, layers of warm water vapor and cool hydrogen gasses mix. The storms take time to develop because water vapor is much heavier than hydrogen so it is normally positioned below the hydrogen fog. This gives the elevated hydrogen gas time to cool. Once it cools down enough, it becomes more dense which causes it to sink into the warmer water vapor. The two mix and voila!, a Saturnian thunderstorm is born. The storm also kicked up hydrocarbons from the lower atmosphere which surprised scientists.

 

Although Saturn probably can’t harbor life, two of Saturn’s moons, Titan and Enceladus, are ripe with the ingredients. The Cassini spacecraft made numerous orbits around Titan and even sent a probe (Huygens) down to the surface. Titan has land features similar to Earth, with lakes, mountains, ice caps, and deserts. The difference is methane and ethane are the chemical building blocks of the complex molecules found on the moon instead of carbon.

 

Enceladus was the biggest surprise to come out of the Cassini mission. This moon is essentially a smaller version of Jupiter’s moon Europa. Both are covered in a liquid ocean topped with a thick layer of ice that surrounds the moon. There is one big difference: Enceladus has hydrothermal vents deep within its oceans, just like on Earth, and these vents violently force liquid through cracks in the ice. The plumes are huge and powerful, extending hundreds of miles into space and traveling at hundreds of miles an hour. The Cassini spacecraft revealed that these plumes are chock full of hydrocarbons, which are the building blocks necessary for life. This tells scientists that there is the potential for life in the oceans of Enceladus and possibly Europa.

 

The other moons that Cassini visited revealed some startling information. Tethys has bright arcs of light which can only be seen at infrared wavelengths. Scientists are puzzled as to what they are and what is causing them. The spongy-looking moon Hyperion builds up a static charge as it tumbles around Saturn. Mimas, aka the Death Star Moon, was thought to be a dead world but shows evidence of a liquid ocean underneath its cratered surface. The moon is the same size as Enceladus but has no visible jets or plumes, so the liquid is trapped beneath the surface. Why these two moons are so different and whether Mimas’ ocean is full of hydrocarbons is something scientists hope to study in the future.

 

The potential of life in the Saturnian system is the main reason Cassini’s mission will come to a destructive end. The spacecraft is running out of fuel, meaning that scientists on Earth will eventually lose the ability to control the spacecraft. Our own planet is surrounded by defunct satellites whizzing around our planet– just waiting to crash into other orbiting objects. The scientists in charge of the mission worry that if Cassini were left to orbit Saturn, it could potentially crash into Enceladus. This could introduce foreign microbes and chemicals, devastating any microbial life on the moon or ruining the chances of it ever forming. Instead, Cassini is performing its last dance with Saturn, orbiting the planet so closely that it is between the rings and the gaseous atmosphere. After 22 orbits, the spacecraft will take a dive into Saturn’s clouds on September 15, 2017, sacrificing its own metallic body for the sake of billions of potential life forms on the moons of Saturn.

 

Once Thought Elusive, A Black Hole Will Get A Close-up

 

By JoEllen McBride, PhD

Light can’t escape it but Matthew McConaughey can use it to ‘solve gravity’. They’re the most massive things in our universe but we can’t actually see them. Black holes were theorized by Einstein in the early 1900s and have intrigued both scientists and the public for over a century. Up until recently, we could only see their effects on visible matter that gets too close but an Earth-sized telescope is about to change all that.

 

The term black hole sounds silly but it’s pretty descriptive of this invisible phenomenon. Astronomers call things black or dark because we can’t actually see them with current technology. Black holes form when a star is so massive that its own force of gravity pushes in harder than the molecules and atoms that make it up can push out. The star collapses; decreasing its size to almost nothing. But matter can’t just disappear so this incredibly small object still has mass which can exert a gravitational influence on stars or gases that get too close. If our Sun became a black hole out of nowhere (don’t worry, this can’t happen), the Earth and other planets would not notice a difference gravitationally. We’d all continue orbiting as before; things would just get a lot colder. I guess that’s one way to wash away the rain.

 

So that’s how a single black hole forms but you’ve probably heard references to ‘supermassive’ black holes before. These black holes have masses of many millions or billions of suns. So what died and made that massive of a ‘hole’? Supermassive black holes are not the product of a single object but are most likely formed by the merging together of many smaller black holes. We recently found evidence of this process from the ground based gravitational wave detector, LIGO, which can detect the waves that are produced when two smaller black holes merge. We also know supermassive black holes exist because we have seen their influence on other luminous objects such as stars and gas that’s been heated. We see jets of gas being shot out of the centers of galaxies at close to light speed. There is something incredibly massive at the center of our own galaxy that causes stars nearby to orbit at incredible speeds. The simplest explanation for these observations is that galaxies have supermassive black holes at their centers.

 

But there is another way we could ‘see’ a black hole which was impossible before this year. As stated before, light cannot escape a black hole but anything that becomes trapped in the gravitational well has to orbit for some time before it disappears. So there must be a point where we can still see material just before it’s lost forever; like an object that swirls around the edge of a whirlpool just before falling down the drain. This region is known as the event horizon and it’s basically the closest we can get to seeing a black hole. Currently, the supermassive black hole at the center of our galaxy, named Sagittarius A*, isn’t taking any material in but that doesn’t mean the event horizon is empty. Luminous material can orbit in the event horizon for a very long time, we just need to look at the right wavelength with a big enough camera.

 

The center of our galaxy is 8 kiloparsecs or 1,50,000,000,000,000,000 miles away. To put that in perspective, that’s about 1014 times larger than the distance between the U.S. coasts, 1011 times larger than the Earth-Moon distance and 100,000 times larger than the distance to the next closest star, Alpha Centauri. It’s really far away. The width of Sagittarius A*’s event horizon is estimated to be between the width of Pluto and Mercury’s orbit around our Sun. At its widest estimate, the event horizon of Sagittarius A* would span one-millionth of a degree on the sky. For comparison, the full moon spans about half a degree. So we’re gonna need a bigger telescope– an Earth-sized one.

 

Enter the Event Horizon Telescope (EHT). This network of telescopes operates at radio wavelengths and uses a technique that increases the size of a telescope without having to build a huge dish. The EHT combines telescopes in Arizona, Hawaii, Mexico, Chile, Spain and the South Pole to create an Earth-sized radio dish. A good analogy I’ve found is to picture you and five other friends are standing at various locations at the edge of a pond. You all know where you are located with respect to each other and the pond surface. Each of you also has a stopwatch and placed a bobber in the water directly in front of you. If a pebble gets dropped somewhere in the middle of the pond each of you will wait until you see the bobber start moving and begin recording the time and the up and down motions the bobber makes as the peaks and troughs of the wave passes by. After you’ve recorded enough bobs, you can meet back up with your friends to determine where the pebble was dropped and its size based on the ripples and when they reached each of your respective locations. The EHT will work similarly except the friends are telescopes pointed at Sagittarius A* and the water ripples are light waves.

 

Over 10 days at the beginning of April, these telescopes were in constant contact, monitoring the weather at each site, to coordinate their observations as best they could. Radio waves can usually penetrate everything but the wavelengths that these telescopes were looking at are blocked by water vapor, so clouds and rain mean no observing. On April 15th, they finished their run by successfully obtaining 5 days worth of observations. Now each site has to mail hard drives with their data to a central location, where the images can be properly aligned. The South Pole Telescope can only send out packages after their winter season ends in October, but data is already coming in from the other sites.

 

If everything went as planned, the images should add up to the highest resolution images ever taken of a black hole. This arrangement allows them to measure objects as small as a billionth of a degree. The estimated size of Sagittarius A*’s event horizon is larger than this, so a faint ring surrounding darkness should be visible in the final images. Hopefully, Sagittarius A* was ready for its close-up because humans are eager to see how their own depictions of black holes match up.