Category Archives: Biology

Biology, cancer

A Life in Remission

In the midst of an active research career in astrophysics, in 2008 I was diagnosed with non-Hodgkins Lymphoma, and my world ended.

For the next eight years I learned to live with the cancer growing slowly within me like some creature out of the infamous ‘Alien’ movie series. Annual tests showed the dozens of affected lymph nodes were very slowly growing in size by the millimeter, but with luck none of them would  turn dangerous for a decade or more. But no one could predict when my cancer would ‘transform’ and become dangerously aggressive, requiring immediate chemotherapy. Actuarial forecasts said that the probability of transformation increased by 5% per year, so that after 10 years I would have a 50/50 chance of my NHL becoming aggressive, but it could happen sooner. …or much later. As a scientist, this uncertain diagnosis was devastating.

A scientist conducts research based on the a priori assumption that they will live to see the end of their work and to publish the results.  I just know you are going to say ‘Well, no one knows when they are going to die’, but among those of us who deal with cancer, these kinds of sentiments seem insensitive and a bit flippant no matter how well-intended.

How does one function when one does not know when the monster will spring out of hiding and put the kibosh on your current work? Many of my projects required several years of work, followed by months of writing-up the results and interacting with referees and journal editors to publish the results. You simply cannot muster the stamina to carry-on your research and deal with referees when you are on a short, emotional leash.

Coping with an uncertain future in research

I immediately began to wean myself away from the rigors of research and instead moved into the area of education where NASA had a huge footprint. I won two grants to develop my SpaceMath@NASA resource, which grew every year to become a significant mathematics resource for educators. I even became known in some circles as Dr. Space Math! This was an intensely therapeutic undertaking for me because could write new math problems and design new math books whenever I chose to on my timetable, and if I literally died tomorrow, I would have left behind a complete archive of fun math resources. It was an open-ended commitment that suited my new frame-of-mind, and still made me feel as though I was contributing, intellectually, to a Greater Good: The education of our children.

As the years began to add up, 5…6..7…8  I started to realize that I might be in this cancer frame-of-mind for the long haul. But by this time my hiatus from research, and my ‘advanced age’ of 64, precluded any re-entry into the level of research I had enjoyed in my earlier years. It was very sad to see this part of my career waste away, but considering I was in my peri-retirement years, perhaps as it is for so many other scientists, this transition was inevitable.

In 2016 my NHL became aggressive after eight years of near-dormancy. I was quickly rushed into a course of immunotherapy with a monthly infusion of Rituximab and Bendemustine for six months. At the end, a PET scan showed in November, 2017 that there wasn’t a sign of  the NHL anywhere, and my oncologist, Dr. Bruce Cheson at MedStar/Georgetown University Hospital in Washington DC pronounced me in remission. For the next two years, if there was no further sign of the NHL, he would consider me cured!

All of a sudden my attitude seemed to change almost literally over-night. I was anxious to start new research projects that, at least for now, could be completed in six months or less including writing up the results and submitting to the Journals. I had been out of my own research area for too long, and besides no astronomer at the age of 65 worries about new research unless they are still employed at a stable faculty or government job…which I was not. But I did have a part-time position at NASA working on citizen science activities. I was also involved in some very fun research trying to determine how well smartphones performed as scientific data-gathering sensors. That was starting to generate a pipeline of short-term projects culminating in several papers every year. But now that I was in remission, I could start to think about more complicated projects to tackle once again.

So I, basically, have come full circle in research having wandered for eight years in the dreary and uncertain desert of non-research work.

It’s good to be back!!

 

Astronomy, Biology, Space Travel

Exoplanets Galore!

***This Blog was updated in 2023 with new data. Visit Exoplanet Update. 

The year was 2001 – The first of the new millennium. It was also the year astronomers reached a historic milestone: They had catalogued more planets orbiting distant stars than the eight we knew about in our own solar system!

The first of these was discovered in 1988: A Jupiter-sized world orbiting the star Gamma Cephi A at a distance of 45 light years from our sun. Since then, well over 3,600 ‘exo’planets have been discovered using many different detection methods both on the ground and in space. We are truly living in a very different age than we experienced only a few short decades ago. We no longer have to speculate whether other planetary systems exist across the universe. We now have the technology and a growing catalog of examples to prove our solar system is not alone in the universe!

One of these detection methods is the Transit Method. As a planet passes in front of its star as viewed from Earth, the brightness of the star dims by an amount equal to the ratio of the planet’s circular area to the star’s circular area. For example, a Jupiter-sized planet has a diameter of 143,000 km while a sun-like star has a diameter of 1.4 million km, so the ratio of their areas is 1/100. As this exoplanet transits the disk of its star as viewed from Earth, the brightness of the star will dim by 1%. By measuring the time between successive transit ‘dips’ you can deduce the orbit period of the planet. From the orbit period and the mass of the star you also obtain the distance between the star and the planet. Once you have this information, you can estimate the surface temperature of the planet and its average density (rocky planet or gas giant). In the example below, the orbit period is 4.887 days and from the amount of dimming ( 0.7%) the ratio of their areas is 1/142, and planet’s diameter is 1/12 the diameter of its star.

To take advantage of the transit method on a large scale, NASA launched the Kepler Observatory in 2009. Using a super-sensitive digital camera, it took a picture of the same star field in the constellation Cygnus every minute and captured brightness information for over 150,000 stars similar to our sun. Over the course of its survey, now in its eighth year, it has discovered 4,496 exoplanet candidates of which 2,335 have been verified by independent study. These statistics now show that virtually all stars in the sky have at least one planet in orbit around them, and about 1 in 20 have Earth-sized worlds!

What was entirely unexpected was the diversity of exoplanet types, and orbits about their parent stars. Our solar system offered as templates the small rocky Earth-sized worlds of the inner solar system, the two gas giants (Jupiter and Saturn) and the two ice giants (Uranus and Neptune), but among the thousands of worlds discovered so far, a vaster array of possibilities have been found.

There are super-Earths over three times as large as our world apparently fully covered by deep oceans (Kepler 22b). There are hot-Jupiters that orbit their stars in a matter of hours, and swelter at temperatures of thousands of degrees (51 Pegasi b). Some planets have ‘water cycles’ in which silicate rock evaporates from their surfaces, condenses in clouds, and then rains droplets of lava back to the surface (COROT-7b, Alpha Centauri Bb, Kepler 10b). The cloud-shrouded super-Earth GJ 1214b is so hot that its clouds could be made of zinc sulfide and potassium chloride! One exoplanet is so close to its star that it is literally evaporating before our eyes, leaving a huge comet-like tail of gas in its orbital wake (HD 221458b).

The thousands of exoplanets detected by the transit method are especially intriguing. From Earth, as the exoplanet passes in front of its star, some of the starlight passes through the exoplanet’s atmosphere. Various gases in the atmosphere absorb selected wavelengths of this light and leave their unique fingerprints behind for distant astronomers using spectroscopes to study. So far among the dozen or so worlds examined, atmospheres rich in water vapor, carbon dioxide, methane, sulfur and other common molecules have already been found. This figure shows the spectrum of the exoplanet Wasp-19b and signs of methane (CH4) and hydrogen cyanide (HCN) – a lethal mixture for humans to breathe! Future ground and space-based observatories will be able to detect the molecules in thousands of exoplanet atmospheres, but this is no idle scientific pursuit. Living systems on a planetary scale sculpt their atmospheres by creating free molecular oxygen, so if we ever detect an exoplanet atmosphere rich in oxygen, it will be a major discovery of life in the cosmos beyond our own Earth.

Another aspect of the search for Earth-like worlds is to find exoplanets about as large as Earth that orbit their stars in what is called the Habitable Zone (HZ). In this range of orbital distances from the exoplanet’s star, the surface temperatures would allow liquid water to exist. In our solar system, this zone is located between the orbits of Venus and Mars, and Earth is smack in the middle of it. Currently, the various surveys have identified 13 exoplanets that are not only Earth-sized but are within their star’s HZ. The closest of these is GJ 273b at a distance of 12 light years! But there are complicating factors to finding an exact twin to our Earth upon which we might also hope to discover a living biosphere.

If a planet in the HZ has too much carbon dioxide – a potent greenhouse gas – its temperature would be more Venus-like and it would be a desert world or worse. If the exoplanet had significant traces of common gases such as hydrogen cyanide or methane, it would be unbreathable for humans though some extremophile bacteria on Earth thrive in such environments.

Another thing to think about is that an Earth-like world could be in orbit around a Jupiter-sized exoplanet in its star’s HZ. Even though we do not directly see the Earth-sized world there could be several of them as satellite worlds of larger exoplanets. The Jupiter-sized exoplanet WASP-12b appears to have an ‘exomoon’ with several times the mass of Earth. We know of hundreds of Jupiter-sized exoplanets orbiting in the habitable zones of their stars. We can no longer discount the possibility that their exomoons may be Earth-like though currently undetectable.

So far we have had to detect and study exoplanets indirectly from transit and spectroscopic data, but in a growing number of cases we can actually directly see these worlds as they spin around their stars. In 2008, the bright star Fomalhaut was observed by the Hubble Space Telescope and revealed a small planet among the debris of its dense disk of gas and dust. In another instance, the young star HR 8799 was observed by the Keck Observatory in Hawaii and revealed four massive planets (HR8799 b, c, d and e) in orbit. This is only the beginning of direct-imaging studies as we enter a new era of exoplanet studies.

What will the future bring? The spectacular success of the NASA Kepler mission is just the beginning of new missions to come that will discover thousands of new exoplanets. The NASA, Transiting Exoplanet Survey Satellite (TESS) will be launched in 2018 and will perform a Kepler-like survey of the 500,000 brightest stars in the sky. This survey will double the number of known exoplanets and include hundreds of additional Earth-sized candidates. At the same time, the Webb Space Telescope will be launched and among its many research programs will be ones to study the atmospheres of known exoplanets and Earth-sized candidates.

Check back here on June 18 for my next blog!

Astronomy, Biology

Synthia

We can micro-miniaturize electronics by making their components smaller and smaller, but what about living organisms? Humans consist of over 20,000 genes coded into a billion-nucleotide molecule called DNA. That’s a lot of information for a complex organism like humans, but when it comes to genome size, a rare Japanese flower, called Paris japonica, is the current heavyweight champ, with 50 times more DNA than humans. But what is the smallest number of genes and nucleotides needed to create a living system?

Researchers call this the Minimal Genome, and it is what you get when you take a simple organism and strip away all of the non-essential and duplicative genes, leaving a bare minimum behind to spawn a healthy living system. To find one of these organisms in Nature, one would think that you have to search far and wide to find it among the millions of organisms on Earth. Luckily, a prime candidate was found much closer to ‘home’!

Following an intense multi-decade search, the current champion organism with the fewest naturally-occurring genes is a rather dangerous pest called Mycoplasma genitalium (M. genitalium). MG is a sexually-transmitted disease  that doctors have known about since the 1980’s and more than 1 in 100 adults have it. It causes urethritis and pelvic inflammatory disease among other symptoms. It is also a bacterium with only 482 genes among 582,970 nucleotides.

By 2008 the researchers had artificially synthesized the complete 482-gene, circular chromosome of M. genitalium, however, M. genitalium is a slow-growing bacterium so by 2010 the research switched to another simple organism called M. mycoides with a faster reproduction cycle. They were able to synthesize the 1-million nucleotide DNA of this bacterium and transplant it into the body of yet another bacterium called M. capricolum, which had been scrubbed of all its DNA. The new genome quickly took over the cell and was dubbed Synthia, but it behaved exactly as M. mycoides even though it was entirely synthetic. It had been created from a computer record of its sequential gene compliment and a set of chemicals, so it truly was the first lifeform whose parents were a computer and a set of chemical pumps!

Syn 3.0 – (Credit: Mark Ellisman/National Center for Imaging and Microscopy Research)

Following a tedious process of trial-and-error where over 100 different analogues with different minimal DNA sets were created, most non-viable, the creation of a new synthetic bacterium, Syn. 3.0, was announced by Nobel laureate Ham Smith, microbiologist Clyde Hutchison, and genomics pioneer Craig Venter at Harvard University in the journal Science on March 25, 2016.

Although Syn 3.0 only had 473 genes, amazingly, the function of 149 of these remains unknown. Some create proteins that stick out from the bacterium’s cell wall but their functions are unknown. Other genes seem to be involved in creating proteins that shuttle molecules in and out of the bacterium’s cell wall, but the nature of these molecules and their role in the cell’s metabolism is unknown. The artificial genome was also reorganized using a computer algorithm to place similar genes near each other – like de-fragging a hard drive, but this did not have any obvious effect on the bacterium.

In at least one case, a ‘watermark’ sequence was inserted into the genome of an earlier synthetic bacterium called M. laboratorium. The 4 watermarks are coded messages in the form of DNA base pairs, of 1246, 1081, 1109 and 1222 nucleotides respectively, which give the names of the researchers, and quotes from James Joyce, Robert Oppenheimer, and an especially relevant one by Richard Feynman: ‘What I cannot build I cannot understand’.

Is M. Genitalium really the smallest organism? Probably not, but it depends on how you define such minimal organisms. Since its genome was sequenced in 1999, we now know of five additional bacteria with even smaller genome sizes. The smallest of these is Candidatus Hodgkinia cicadicola Dsem with only 169 genes, however like the others this organism’s genome is supplemented by the host cell’s genome so it acts more like an organelle than a free-standing organism.
 M. genitalium is classified as an intracellular parasite and cannot exist by itself in the biosphere. It requires a host system such as the human urinary tract to provide the environment to sustain it. For truly free-standing organisms that can actually live by themselves and reproduce, the smallest of these is currently thought to be Pelagibacter ubique, which was found in 2002. It makes up 25% of all bacterial plankton cells in the ocean. It also undergoes regular seasonal cycles in abundance – in summer reaching ~50% of the cells in the temperate ocean surface waters. Thus it plays a major role in the Earth’s carbon cycle! Its genome was sequenced in 2005 and consists of 1,308,759 nucleotides forming 1,389 genes. Its genome has been streamlined by evolution so that it requires the least amount of nitrogen to reproduce (a scarce resource in the bacterium’s ocean environment). The base pairs C and G are nitrogen-rich, with a total of 11 nitrogen atoms between them. A and T are nitrogen-poor and have only 7 nitrogen atoms between them. All other environmental factors being equal, instead of 50% of the genome containing A and T, a whopping 70% does. Somehow, this bacterium has found a way to find alternative ways to create genes that are essential for life by avoiding the ‘expensive’ alternatives. Over billions of years it optimized itself to the current low-nitrogen compliment.

Why is all of this important? Why is synthetic genomics such an important research area? Because it is a direct way to identify how hundreds of genes work together to create viable living systems: their skeletons, metabolisms and reproductive strategies. For astrobiologists, it is a glimpse of what alien life might look like when it is pared down to its absolute essentials but still behaves as an independent system rather than a viral symbiont requiring a pre-existing host. Also, once we know what a basic viable bacterium host looks like, genetically, we can systematically add to this genome other factors of interest to us. We can explore what the process of epigenetics looks like as various environmental factors are added to switch on and off genes. Above all, it is the inevitable questions to come about the essential mechanism of life that will be the most exciting to watch develop!

Check back here on  Tuesday, June 6 for the next essay!