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An Abandoned Sailor’s Infirmary in NYC Where Cholera Bacteria Was Discovered
Hello clever TWIM ers,
A rather urgent detective story that TWIM might be interested in talking about. People in the area must be very spooked.
Neva in Buda
Deadly disease outbreak in Wisconsin baffles public health officials
A common and usually harmless microbe is causing a mysterious cluster of deadly bloodstream infections in Wisconsin.
Hi Docs, this cnn article gives some info on a continuing Elizabethkibgiam outbreak.
Rarely seen blood infection outbreak continues; source remains mystery
The rarely seen blood infection Elizabethkingia has been found in a Michigan resident. It has sickened dozens in Wisconsin since November. Read the full story
Elizabeth King (used to be Flavobacterium)
Guys isn't gender neutral it's gender absorptive. It's used the same way it became standard over the last few hundred years to use he as a general third person singular pronoun (before that they was acceptable). Just because some women are OK with it doesn't mean the rest of us can't be annoyed by it. If your students will call a specific, individual woman a guy then I guess I'm wrong and it's honestly becoming gender neutral. But I never hear anyone doing that.
Inspired by William:
Greetings from Berkeley where miracle March (water-wise) was perhaps half a miracle, but that is definitely better than none. At least we will not run out of water this summer.
I found this quasi-synthetic biology result to be very interesting on several levels.
First, it does not surprise me that Craig Venter was the one to do it. Thirty years ago I ran the computing group that supported the DOE Human Genome center at LBNL when it was run by Charles Cantor. The focus was on sequencing long fragments which was hard but the reassembly was relatively easy.
Venter went off on his own and said that shotgun (as I recall the term) sequencing was the way to go: make lots of short fragments that can be sequenced quickly and then use statistical methods to reassemble computationally. He, of course, was right.
Second, I found it fascinating that "... after 20 years of concerted effort, his group has built - essentially from scratch - the minimal life form.
And in the process demonstrated that we have a very incomplete view of how life works at the most basic level.
However, now that they know the 30% unknowns, they can systematically tackle those genes one at a time to figure out their essential role." (The Atlantic article.)
Even when they infer that function of some of these from looking at similar genes in other organisms where their function is know, they still end up with 17% that are essential to this minimal life form that they have no idea what they do. No idea ... surprising.
Thirdly, "In a parallel experiment that didn't wind up in JCVI-syn3.0 , the scientists reorganized about an eighth of the genome to put genes with similar functions next to each other. Venter called this process "defragging the genome," as one would do with a computer's hard drive. In this parallel experiment, the defragging of that section of the genome didn't seem to harm the organism."
I would have thought that gene placement on the genome would be the result of some important optimization evolution, but that is apparently not the case. (THe San Diego Union article - see the nice diagram of this.) THough this may be the key:" "Despite extensive reorganization, the resulting cell grew about as fast as syn1.0, as judged by colony size," the study said. "Thus, the details of genetic organization impinge upon survival in hypercompetitive natural environments, but the finer details are apparently not critical for life." (San Diego Union) So the organization may only be non-critical in a very benign environment.
Fourthly, I like this: 'This philosophy of learning basic biology by building stuff is the best bit of the syn3.0 story, says Drew Endy from Stanford University. “Too often in biology we end up with only data, a computer model, or a just-so story. When you actually try to build something you can’t hide from your ignorance. It either works or it doesn’t.” (The Atlantic article.)
Anyway, it would be interesting to hear you take on this.
The ARS Technica article (http://arstechnica.com/science/2016/03/minimalist-genome-only-473-genes-synthesized-and-used-to-boot-up-a-cell/) gives some of the experimental technique and a pointer to the scientific paper ( Science, 2015. DOI: 10.1126/science.aad6253 )
The best of the popular articles is this San Diego Union Trib. article. (Unsurprisingly - given all of this sort of activity in the San Diego / La Jolla area - they have a lot of good molecular biology articles.)
J. Craig Venter Institute unveils bacterium with smallest functional genome
Everyone at TWiM,
I wanted to thank you again for the interest you and your colleagues have taken in our Cell Host & Microbe paper "Fungal Mimicry of a Mammalian Aminopeptidase Disables Innate Immunity and Promotes Pathogenicity," which was expertly reviewed in your most recent podcast. It was wonderful to hear someone as enthused with our findings as we were. However, I just wanted to clarify a minor point. While it is accurate that Alana completed most of the neutrophil work for this paper, for the past two years now my own research has primarily focused on further teasing apart how B. dermatitidis modulates neutrophil function by acting on other cytokines and chemokines using both neutrophil-like cell lines and peripheral primary neutrophils. Again, I very much enjoyed the podcast and appreciate the interest in our work.
Ph.D. Graduate Student, Klein Lab
University of Wisconsin-Madison
Dear TWiM Team,
In episode 124 (Fungal Parasites) a listener asked if quorum sensing was involved in development of abx resistance.
Dr. Melanie Blokesch studies how quorum signals induce competence in V. cholerae. This phenomenon particularly happens in aquatic environments when V. cholerae forms biofilms on chitinous surfaces. These aquatic biofilms can incorporate multiple V. cholerae strains, and the subsequent DNA transfer between strains could promote the spread of abx-resistance genes. However, I was unable to identify a paper that was specifically tracking the movement of Abx resistance genes between species.
Really enjoying the podcast, looking forward to the next one.
Each year, we recognize World TB Day on March 24. This annual event commemorates the date in 1882 when Dr. Robert Koch announced his discovery of Mycobacterium tuberculosis, the bacillus that causes tuberculosis (TB).
Too many people in our country and around the world still suffer from TB. Anyone can get TB, and our current efforts to find and treat latent TB infection and TB disease are not sufficient. Misdiagnosis of TB still exists and health care professionals often do not "think TB."
The theme of World TB Day 2016 is “Unite to End TB” CDC and its domestic and international partners, including the National TB Controllers Association, Stop TB USA, and the global Stop TB Partnership are working together to eliminate this deadly disease. But we need your help.
# # #
In some areas of Jersey City, every day is Tuberculosis Day.
Also from Anthony:
Above is the Link to the artist's Site for the Petri dish art.
This image was posted on Facebook by Kim Dallesandro, the wife of the Warhol star Joe Dallesandro. I don't know where it's originally from.
Hi Drs. Racaniello et. al,
I have a specific case study of Yersinia pseudotuberculosis which I think may be of interest to you or listeners:
I recently acquired a toddler. At the time the toddler arrived to my house, she was 18 months old, eating only formula from a bottle, was not toilet trained, and did not have a habit of putting things into her mouth. Her previous living conditions are unknown, but it is safe to say they were generally unclean. Her primary caregiver was a vegetarian and an IV drug user.
The toddler had frank diarrhea 6+ times a day upon arrival. Also upon arrival she was switched from formula to "real food" and water. I took her to multiple doctors regarding the diarrhea who across the board suggested that she had a gluten intolerance or a lactose intolerance.
As an owner of multiple dogs who drink out of woodland puddles, I know infected poop when I see it.
After a string of doctors and taking a watch/wait approach, I finally walked into an ER and demanded that a doctor test her for parasites (after lying to the doctor that I had, in fact, removed her from gluten for a period of 4 weeks), and low and behold - the toddler had Yersinia pseudotuberculosis, was treated by antibiotics for about 3 weeks, and is now ~6 months out and 100% symptom free.
A happy ending to a sad story.
I want to apologize for not writing much lately due to excessive "grad studenting" (yes, this is now a verb). However, I would like to request that you please discuss the hyperthermophile microbes of Peru's Boiling River. I assume you have seen it all over the news last week. I listened to the audiobook and was very impressed. I am anticipating another potential Taq polymerase, or something even more mind-blowing, to come out of this and would love to hear what the learned TWiM hosts have to say about it and the interesting (and potentially academically risky) stance of Andres Ruzo. Back to excessive "grad studenting" now.
I think ticks are such good transmitters because they stay on you, feeding, for hours to days.
hello i am Gargee from India and i am a regular listener of your podcasts. I have a question, can development of antibiotic resistance be related to quorum sensing? Have any studies been made on this topic?
Washington Post - Plague alive and well in Madagascar
Plague victims’ corpses are to be buried immediately to prevent the spread of the disease. This means that they may be interred near a city hospital, instead of in the family crypt. But families will go so far as to stealthily unearth their loved ones to bring them back to their own villages for burial. Plus, there is a chance that families may anticipate not being able to bury their family members properly and decide to not bring their relatives to the hospital at all, said Ken Gage, chief of Flea-Borne Diseases Activity at the CDC. Among officials’ tactics is burying the corpses with concrete tombs to try to discourage the unearthings, Werner said.
Madagascar has seen lower numbers of deaths from the plague in the past two years, but an alarmingly higher rate of contracting the pneumonic form of the disease — the kind that is airborne and can kill you in 24 hours.
Hello professors TWiM,
Thanks for the great podcast. I have often wondered why we so frequently prescribe single antibiotics to patients. At this point we know that bacteria are rapidly evolving resistance. It strikes me that this is exactly the same problem as we have with HIV infections, with the primary difference being a question of the speed of evolution. Human immunodeficiency virus evolves very fast, to the point that resistance evolves within just a few years (or less) in a single host. With bacteria, the exact same process is happening, but bacteria are much larger and slower evolving, so the process takes decades and many hosts. However, the solution is still basically the same: if it takes a decade plus a few million infected hosts to evolve resistance to a single drug, surely it would take centuries to evolve resistance to a combination therapy?
So then the question is: why does this never happen? I recognise that the resistance issue is not only an issue of medical prescriptions, the massive use of single-drug antibiotics in stock animals is probably an even bigger concern, but still: doesn't it seem that using a triple therapy of antibiotics would be more effective for the patient, as well as being better at preserving our antibiotic supply?
I recognize the immediate response would be: we don't give more drugs than we have to. My answer to that is easy: we have to, we are running out of antibiotics. The next obvious response is that antibiotics have side effects and that this means you should minimise their use. Is that the main reason that we don't do this? Is there a reason we can't give a single pill with multiple antibiotics in it and just give anti-nausea and anti-diarrhea medicines to the patient to take as needed? The side effects of a single antibiotic are primarily due to the death of so many bacteria in the gut, would adding two more antibiotics to the mix actually make those symptoms that much worse? I have no idea, but I would really like to know.
Thanks so much again for your fantastic podcast.
All the best,
Greetings TWiM crew!
I recently learned of a new game (currently getting ready for Alpha and crowd funding) where players will edit microbes at the genetic level and pit them against microbes created by other players. The game is called CURE, and can be found here: http://curethegame.com/
It claims to be accurate based on current scientific knowledge, and to have been reviewed by teachers and scientists.
Being a gamer and super interested in Microbiology, this was right up my ally and I figured I probably wasn't the only TWiX fan who would be interested in this.
QA Analyst 3 : Hearthstone
Tardigrade creed art
Hi Docs, regarding TWIM #120 and tubeworm metamorphosis stimulated by a bacterium, what a fascinating observation. Dr. Lynn Margulis and Dorian Sagan in their book, “Acquiring Genomes”, have a chapter titled Seaworthy Alliances in which Dr. Donald I. Williamson’s work is quoted in which he claimed that invertebrates owed their transformations from larval forms to radically different looking adult forms to “acquired genomes”. He did experiments to cross Invertebrate sea urchin fathers (Echinua escalentus) with Chordate mother sea squirts (Ascidia mentula). “Not only did the fertilized eggs survive this bizarre coupling but they developed fully paternal larvae, the immature forms called plutei.” … “Some of these weird hybrid forms survived up to 90 days from hatching.” There’s much more detail and he begged for some independent group to try the same experiments but I’ve never heard more of this kind of work. Margulis’s entire book was dealing with the question of how some animals develop with wildly different phases, for example from embryo to larva to pupa to adult. I wonder if the observation of the bacterium stimulating a tubeworm transformation will also stimulate more work in either expanding on or correcting the theory of acquired genomes in higher forms of animals. Have you any thoughts on the theory of acquired genomes? We know that many life forms acquire viral DNA (and bacterial DNA?). How about higher forms of acquired DNA? Thanks,
Listen to TWiM
Right click to download TWiM#122 (46 MB .mp3, 63.5 minutes).
With regard to the question about culturing gut microbes from Drosophila:
I was lucky enough to take a sabbatical in the lab of Dr. Angela Douglas (http://angeladouglaslab.com/) in the Fall of 2012, where I worked on the gut microbiota of Drosophila. Her lab found that the diversity of gut microbes in lab-reared Drosophila is quite low, comprising just 5-6 taxa, almost entirely Lactobacillus and Acetobacter (Wong ACN, Ng P and Douglas AE, 2011. Low diversity bacterial community in the gut of the fruitfly Drosophila melanogaster. Environmental Microbiology 13: 1889-1900. Pubmed link). These are easily culturable, although they grow better in low-oxygen environments. Cultivation techniques for these bacteria can be found here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3911109/.
Hope that helps!
Dr. Jeanne Kagle
Professor of Biology
169 Grant Science Center
Mansfield, PA 16933
Happy New Year (And Happy Birthday to Vincent).
I have to say it was good to hear a TWiM (118) where I understood every word! :) Having been a mushroom collector in my time, it was like revising the morphology section--right down to the sterigmata!
I had often wondered how the spores managed to 'stop' and fall down between the gills, but perhaps the air viscosity is sufficient as Elio says. A further point to note may be that the mushroom cap is elevated on the stipe so as to get the spores above the lamina airflow that hugs the ground, close to, and into the turbulent air that carries them aloft. [You might also observe that the gills are always gravitationally aligned, even if the stipe is bent: the spores have to be able to fall down unimpeded.]
Where it comes to the assertion of the importance of fungal spores to cloud formation, I have to refer you back to your programme on EHux, and other phytoplankton, where we were told that the production of dimethylsulphide as a result of breakdown of sulphur-containing metabolites, was the key to controlling the World's weather, as the DMS leads to the formation of sulphate aerosols that act as nucleation foci for water droplets, much as the fungal spores are mooted to do in today's podcast.
Without reading into this before writing whilst it's still fresh in my mind, I would suspect that, as they are derived from molecular processes, the aerosol particles may be smaller than even the fungal spores, and give more nucleation foci per m3 than obtained from even the large number of spores mentioned.
So, on the whole, I think I am more inclined to stick with the phytoplankton than the mushrooms in importance as rainmakers, though I think that almost any dust particle, including spores, will act as a nucleus too...
...Or do the sulphate aerosols need particles to condense on just as the water vapour does? :/
Many thanks for all your great podcasts, and I look forward to many more in the New Year, especially as I have now caught up with the story so far on TWiV, TWiM, and TWiP.
All the best,
TWIM is one of my top 3 podcasts-an excellent way to relax-thanks for a great job. I enjoyed Bullers drop, fungal spore ejection and discussions of potential life on MARS but what about some discussion of life in Earths subsurface, where most microbes on/in Earth live, at depths down to several kilometers and at very low metabolic rates! They play a major role in geochemical cycles and natural resource formation. The paper below is an old one from Casey Hubert at UoC and talks of bacterial spore transport and so on. I think survival and transport of micro-organisms within and between planets would make an interesting episode for readers. Discussion in more detail of microbial survival on interplanetary transport and landing via meteorites would also be interesting, which you touched on in the spore/MARS episode.
Thanks and best wishes. cheers steve
Hubert, Casey, Alexander Loy, Maren Nickel, Carol Arnosti, Christian Baranyi, Volker Brüchert, Timothy Ferdelman et al. "A constant flux of diverse thermophilic bacteria into the cold Arctic seabed." Science 325, no. 5947 (2009): 1541-1544.
Dear TWiM team.
I saw this advert for a two year postdoctoral position for a microbiologist at the UK Centre for Astrobiology, University of Edinburgh and thought it may be of interest to other listeners.
I do not have any connection with the University of Edinburgh other than having taken their Coursera astrobiology course.
Here is the description:
A two-year STFC-funded PDRA position is available at the UK Centre for Astrobiology, University of Edinburgh to investigate the behaviour of microorganisms in space, using the International Space Station. Your work will involve understanding the effects of extreme space conditions, including microgravity, on microbial communities and use these data to advance our understanding of how we can look for biosignatures of life elsewhere and develop new methods to look for those signatures. You will work to help develop new experiments using orbital and space facilities. You will lead both laboratory based and theoretical research to apply this research to STFC science. You should also have an interest in technology transfer. Working at the interface between biology and planetary sciences (astrobiology), at Edinburgh, your responsibilities will include advancing work on space experiments and the use of space facilities to carry out research. You should have a PhD in biological sciences.
You will be a member of the UK Centre for Astrobiology. You will play a wider role in developing astrobiology. This includes working on our ‘Astrobiology in the Classroom’ initiative which, through the Astrobiology Summer Academy, involves developing lesson plans with primary and secondary school teachers to use astrobiology as a vehicle to advance science education in the UK. We seek a self-motivated scientist who will play an active role in creating links with space agencies and other astrobiologists. You will also be responsible for supervision, training and oversight of other staff.
The start date is 1 April 2016. This is a fixed term 2-year position.
You can apply here: http://www.ed.ac.uk/human-resources/jobs
The job vacancy is 035130
First of all, thank you for reading and commenting on my talmudic question about unleavened bread. I hope that it got some of your listeners thinking.
Second, I had a few thoughts that I thought might or might not help amplify your discussions in this episode.
1) Thanks for the article of amoebic pack hunting. I think that I’ve heard of similar tactics with other microbes. Dr. Racaniello kept referring to nematodes in a negative sense. One nematode function that he particularly picked on was “parasitism”. I’d like to point out that nematodes are as diverse a group as they are because they occupy nearly every ecological niche available somewhere in the world. While many of them are quite nasty, nearly all are valuable contributors to the environment. Because of the differences in scale, we tend to think of plant-eating nematodes as infestations while we tend to think of plant-eating ungulates as cattle. Also, think about the difference (or lack of differences) inherent in nematodes that graze on bacteria and nematodes that graze on algae. Thinking on their level is probably one of the most fascinating things about this group.
2) One of the reasons that I have a small interest in nematodes is exactly their occupation of so many ecological niches. Dr. DesPommier (if he hasn’t already heard of this) may be interested to know that Dr. Sharanbir S. Grewel (formerly of the Ohio State University) has been working on a method to measure soil health by microscopic assays of nematodes in a soil sample. Unlike many systems that have used nematodes to generate soil health indices, Dr. Grewel’s methodology relies only on identifying the categories of mouth types in the sample’s nematodes. Since these mouth parts are fairly characteristic for the nematodes’ soil services, they are much quicker and easier to identify that species. The numbers and ratios of the service (mouth) types can give a fairly good idea of how “alive” and diverse the soil is. Unfortunately, Dr. Grewel left OSU before I could work with him to develop a gardener’s guide to using this technique and I have not seen that he has published the basics of it yet.
3) Thanks for the article on fungal spore dispersion biophysics as well. I have to say that I disagree with their assessment of evolutionary advantage. I think that:
A) being a point of droplet nucleation would help ensure that the spores could be carried in the clouds further than naked spore because naked spore would be subject to more chaotic and, therefore, shorter overall paths. Genetic dispersion can be an advantage.
B) In the open atmosphere, spores are vulnerable to UV exposure. It seems to me that thicker aqueous coatings would reduce UV exposure and, again, portage inside a cloud would provide some further protection.
C) Being a rain droplet nucleation site would also help ensure that a spore lands with an initial bolus of water to help initiate sporulation. This would take advantage of a short-term survival strategy that requires only an initial exposure to water. It might be that non-ballistosporic spores take advantage of longer-term survival strategy of initiating sporulation only after water has been available long enough to make a water steady state more likely.
4) I suspect that there is a lot that we can learn about hydrophobic / hydrophilic metamaterial surface design from studying these spores.
5) Much of water droplet formation seems to be based on nucleation site chemistry. That might be the mannitol. That might be part of the surface structure of the spore itself. It might be a combination. I saw little reference to this chemistry in the paper. If they aren’t already in talks with someone, then I would suggest that the authors need to collaborate with a meteorological chemist to look at the surface chemistry of the aquated and non-aquated spores more closely. If this hasn’t already been studied in some detail, then the estimates of atmospheric spore concentrations suggest that it should be. The fact that spore surface chemistry changes may be a point overlooked in previous nucleation site studies.
6) In addition to studying spore effects on droplet nucleation in a cloud chamber (I believe that that’s what the warehouse-sized buildings are called, not the atomic tracing chambers), I would suggest that a potentially less expensive test would be a correlational study between the atmosphere and cloud concentrations of the two types of spores versus rain formation based on mannitol biotracer monitoring might be possible.
7) To chime in on Chris’ martian pathogen question, I would say that it might be possible even if there wasn’t a microbial exchange between Earth and Mars. As long as the martian life-form requires carbon, oxygen, nitrogen, and water, I could envision a decomposer-type organism which doesn’t so much hijack the host body but chemically decomposes it and scavenges the chemically-shattered remnants. It could be something along the lines of acid-based hydrolysis which would have the added advantage of liberating needed minerals in the martian soil. The bigger question would be if any extremophilic microbial survivors on Mars could survive the (relative) superabundance of water in Earth organisms. Such extremophilic organisms might also grow so slowly as to be swamped out by the abundance of life in most Earth organisms. On the other hand, if a dead body were left on Mars and mostly dried out, then those organisms would be all over the body like bone worms on a whale carcass in the deep blue terrestrial sea.
Thanks for another stimulating episode!
What Happens to Your Microbiome If You Own a Dog
Dear Vincent, I have a fun question for your panel about Mars
I was watching NASA talk about how Mars' atmosphere was stripped away and was wondering about Mars bugs. Here are some fun (probable) facts I learned.
When life was starting on earth, 3.8 billion years ago, Mars had an atmosphere about the same size as earth and had liquid water in lakes and streams all over the surface. So Earth and Mars look a lot alike. At 3.5 billion years ago, Mars' dynamo cooled down and its magnetic field stopped. Then the high solar activity of the sun sent strong solar winds that stripped away Mars' atmosphere, and Mars turned into the icy desert we see today. The one place NASA would look for microbial life today is in Mars' aquifers. If they found some, they would like to know if the genetics are essentially different between Mars and Earth
So let's assume that there was some cross pollination between planets when both were watery, by asteroids throwing Mars and Earth rocks back and forth. My question is; would it be possible for Mars microbes and viruses to infect Mars colonists or would the genetics be too diverged after three or so billion years. Will Martians have to put up "Don't drink the water!" signs.
Here is another one of those articles I find a little strange but what do I know....
I guess it kind of makes sense but I would never have thought of this. I bet you already know about this, don't you?
The rains have returned to Seattle. Yippee!
I've been an avid listener off and on regular for many years since my undergraduate days! I started off learning about viruses from you and now love to listen for interesting tidbits on other microbes! I work in Mycoplasma pneumoniae and my graduate school has one of the largest mycoplasma research groups in the US!
I think you've discussed the synthetic genome cell before (a Mycoplasma species!), but I don't think that I've seen a full session about the smallest known self replicating prokaryotes! I'm a bit biased, but I know some wonderful researchers who would LOVE to do a podcast if there would be interest!
Keep on being awesome and thanks for making my bench time entertaining!
I've been listening to TWIM for the last few months during my more monotonous lab tasks and have learned so much more about microbiology in systems I'm not familiar with. I would have never thought to read some of the papers shared on the show. However, as a plant pathologist, I keep waiting for the day you put us on the map and bring one of us on! I've only been listening since TWIM #87, so maybe I missed it. If not, I know Michele lives about an hour southeast from a university with a pretty decent plant path department.
Though exposure to Aspergillus by immunocompetent people, generally is without drama, that's not true for penguins. Air quality is a big question in maintaining these birds in captivity.
If climate change brings an increase in Aspergillus spores to the arctic, this won't be good for penguins.
# # #
Air quality: Penguins as a group are highly susceptible to air-borne fungal infections. For this reason, the air quality in an indoor penguin exhibit should be optimal. Airflow, fresh air exchange, and filter capacity should be researched to provide the cleanest air possible. Aspergillus fumigatus spores range in size from 2.5–3 microns with other aspergillus species spores as large as 10 microns. In order to remove
these spores from the air, a filter should remove particles in that size range or smaller. If possible sources of aspergillus are external to the exhibit then consideration should be given to reducing fresh air intake and providing a high-quality filter on the incoming air line as well as in the recirculation line. If the possible sources of aspergillus are internal to the exhibit, then a high-quality filter in the recirculating system, a
high volume air change per hour, and increased fresh air exchange—as well as identifying and removing the aspergillus source within the exhibit—should be considered. Collection of regular air cultures in the exhibit as well as the air-handling system is a good practice in preventative maintenance. ...
Drs. Schaechter, Racaniello, Swanson, Schmidt, and Any Guests that I Might Have Missed:
In honor of a section that shows up on your show on occasion, I thought that I might send you an actual talmudic question that I posed and partially answered for another podcast a year or so ago:
Why were the Hebrews unable to take their leavening with them when they left Egypt under Moses’ leadership?
During the seven days of Passover (the comemortation of the Exodus), Jews are forbidden to eat chametz. Although often translated as "leavened bread” (the word seems to derive from a root for “sour”, indicating that it was a sourdough-type food), the word is probably better translated as “foods or drinks containing leaven” (Exodus 12:15) which includes beer (the production of beer and bread were intermingled in Ancient Egypt and, probably, most of the Ancient Middle East). Why bring this up on TWiM? because chametz is the result of se’or or microbial fermentation. What could be more appropriate than an actual talmudic question about microbiology?
Now, Exodus 12:15 provided the injunction against leaven - “For seven days you shall eat matzeh” (matzeh is unleavened bread, flour and water mixed and baked within 20 minutes, not enough time for yeast production to kick in) but not the reason. A reason was given in Exodus 13:8 - “And you shall explain to your son on that day, 'It is because of what the Lord did for me when I went free from Egypt.’.” - but, honestly, that isn’t much of a reason. Part of another reason was given in Exodus 12:34 where it stated that “they took their dough before it was leavened” and in 12:39 where it stated that "they baked matzeh of the dough, which they brought forth out of Egypt, for it was not leavened, since they were thrust out of Egypt and could not delay”. That, on its surface, might seem reasonable enough but any of us who have baked bread and / or know anything about bread microbiology know that there is something wrong about this whole situation. If they took their dough with them, then it already contained the se’or (“starter”). The bread might have collapse on them if they waited too long to cook it but they didn’t leave the se’or behind. That could only have happened had they only brought their grain or flour with them and mixed it with water while they were setting up camp and that is not what the text says.
And there is another complication. Exodus 12:39 implied that they couldn’t bring their leavening with them because they were “thrust out of Egypt and could not delay”. In other words, they didn’t have enough time. Yet the Hebrews had sufficient time to gather jewelry from the Eqyptians (Exodus 12:35-36), enough supplies to build the tabernacle and an altar (Exodus 36-38), and their livestock (Exodus 12:32, 38). They even had time to bring their kneading-boards (mish’eret) bound in the clothes on their shoulders (Exodus 12:34). We know that the Egyptians (and, therefore, and Hebrews living in Egypt) used two main types of starter: a baked yeast cake for storage and, basically, a sourdough starter for continuous use. As most people who have dealt with sourdough starters know, these starters, with their often unique tastes, were cherished family possessions being maintained like a family pet and passed down from generation to generation. They were also mobile. Many American prospectors in Alaska in late 19th / early 20th Century kept them as a cherished part of their minimal possessions in their camps. That means that, if the Hebrews had time to gather other possessions, then they had time to pack their se’or and bring it along. In fact, if they brought their dough along, then they were, technically, bringing their se’or.
So, that brings us back to the question of why leavened bread was forbidden during Passover. I propose that the reason was cultural rather than physical (i.e., a matter of time). The Hebrews that left Egypt were depicted as belonging to many tribes. Their journey through the Wilderness was a depiction of their unification into one overall tribe: the Jews. Se’orim (sourdough starters) were cultural heritage. Because they were handed down from generation to generation, they represented the past. Discarding the se’orim and eating matzeh for seven days until they could make more through wild capture was an act of discarding the past as various hebraic tribes and starting a new life as one larger jewish tribe. I suspect that the Rosh Hashanah ceremony of tashlikh - when one tosses bread crumbs into a body of water to cast away the sins of the previous year - is a similar act. Here too, the se’or and chametz serve as symbols of ones past but delving into the connection further is, I fear, a talmudic question for another time.
This might seem a strange excursion for the TWiM podcast but, when I started to piece it together, I found it to be another fascinating example of how microbiology can serve as a scaffold for understanding cultures long-since vanished from the Earth.
Thanks for the podcast,
I just finished listening to Chewates and Coconuts and was so elated to hear about the open access paper comparing the Soybean Oil, Beef Tallow, and Coconut Oil effects on fungal colonization. I am a biologist by education, but I also have quite the “Crunchy” side. If you have ever seen My Big Fat Greek Wedding you may recall that the father figure uses Windex to solve all of life’s problems, and that is me with Coconut Oil. I have several friends in different fields of science and they poke fun at my inFATuation (pun totally intended) with Coconut Oil and often demand scientific evidence for my claims. This is going to be a great addition to my arsenal along with your entertaining and informative podcast! If you ever have the time or desire you should devote an entire tsegment to Coconut Oil and all of its anti-microbial claims! Thank you for the segment and your weekly contributions to science.
Greetings Dr Racaniello and colleagues,
Thank you so much for your wonderful podcast. I am a high school biology teacher and I thoroughly enjoy your discussions of current articles and topics in microbiology. My background is in biochemistry, and your discussions are engaging and keep me thinking about the unseen microbial world that is all around us.
I am currently working on developing a curriculum where students will investigate the Microbiome of drosophila guts. I was fortunate enough to have a lab fellowship in an immunology lab at the University of Massachusetts medical school this past summer where I developed the fly dissection techniques and basic plating. As most of the Microbiome of Drosophia is comprised of Lactobacillus and acetobacter, I used MRS agar and ACE agar this summer but I found the ace agar difficult to work with and I think it will be challenging for my students (plus it contains cyclohexamide which I don't want to bring into my HS classroom). Could one of the panelists recommend some other potential media that I could consider for introducing these techniques to my students?
Again, thank you for the wonderful show and I look forward to future episodes.
Dear TWIM Team,
I have listened to TWIV for a while but just recently added TWIM to my repertoire, so forgive me if this has been addressed in earlier episodes.
Having a background in chemistry and biology with an eye toward human therapeutics (if only in part for funding purposes), I was a amused by the apparent surprise expressed by the hosts at a microbial secondary metabolite being used in human therapy (TWIM #112). I would argue that the majority of small molecule therapies (especially antibiotics and anti-cancers) to date are derived from microbial secondary metabolites, either directly or some having been chemically tweaked for enhanced stability and pharmacokinetic properties.
Chemists are getting better at rational design or the clunky approach of high-throughput screening of random chemical libraries to find new therapies, but 3.8 billion years of evolution has done a lot of work for us.
I found this review paper on the subject which is rather dated, but seems comprehensive and doesn't appear to be behind a paywall.
Always a joy to listen,
Hi Professors TWIM,
I am a recent convert to microbiology and I am preparing to take a medical microbiology course soon. In preparation, I have been reading several microbiology textbooks and getting a little frustrated. Every book starts with a long discussion of the marvels of the gram stain, but yet after a few hours of googling I still can't find the answer to one very simple question: are gram positives and gram negatives monophyletic? From my initial reading it seems that gram positives are a small monophyletic group, and that 'gram negatives' encompasses a massive group of bacteria so large as to be almost meaningless. Am I completely wrong? Do you know of good review papers that explain bacterial taxonomy? Right now I am left wondering if our obsession with the distinction between gram negative and positive is a relic of a pre genomic age. Or maybe I have no idea what I am talking about (likely). I would love to hear your take on this interesting question.
I love all three of your science podcasts, and I keep meaning to get to the vertical farm podcast soon. I have listened to almost every episode of the others though, and I loved them all.
The weather at Stanford right now (10 pm) is 17 °C, humidity 69%, dew point 12° with a cool breeze from the ocean. A lovely evening; although I really wish we would have some rain.
Thank you ask for the wonderful podcasts, they are all a fabulous service to the community and to the public. They are also wonderful good fun.
Thanks for your help,
So if I understand this correctly, this means that the cooling towers spray a mist of the bacteria (with or without amoeba) into the air and that "rains down" and contaminates the air around the building?
This really conflicts with how some sources are saying it has to do with showers http://abcnews.go.com/Health/wireStory/legionnaires-deaths-tied-spray-shower-faucet-33068564 since the cooling towers shouldnt feed into the showers at all.
Could you provide a clarification for me as to what is actually going on? I'm inclined to trust the cooling tower mist idea just because of the source but that's a lot of bacteria you'd need to have raining down...
Thank you for your lovely show. I started with Twiv after taking Dr Racaniello's online virology course, and have since moved to Twip and Twim, all very instructive and pleasant.
Yesterday my daily Twix dose consisted of TWIM 19. During that episode, there was some speculation whether syphilis had been brought to the Americas by Columbus after having surged recently in Europe, or whether he brought it back. I am passionate about history, and the conquest of the new continent has been a rather merciless and bloody one, especially in the 16th century. Viruses and bacteria certainly played a major role in the extinction of native Americans (in the broader sense) as well, although this biological weaponry was not intentional. So this debate caught my attention, as it would be one disease that might have been brought back to Europe as a sort of pyramid's curse.
Jo remarked that the paintings of Hieronymous Bosch often depicted noses affected by syphilis, and suggested that could be an argument that syphilis in Europe predated the discovery of the West Indies. However, Bosch died in 1516, with his birth estimated around 1456. His works are not dated. It is probable that his more exuberant works may have come at a later stage in his life - when he might not have needed to adhere so much to social conventions to sell his works, and after having grown artistically. If syphilis was indeed introduced from the Americas, the grotesque deformations the disease causes may have provided a ghastly inspiration for his marvelous works.
As the recording of TWIM 19 lies several years in the past, I wonder if new research has revealed more about the origins of syphilis, that is, whether it came from the Americas or the old Continent.
I want to thank you all for your continuing effort in making Twix possible. I am sure people around the world have grown accustomed to your voices and expressions, providing them insights, company and joy. I eagerly read STC now, although I must admit that I skip the talmudic questions as they are way beyond my knowledge level.
Sunny greetings from Nicaragua where it now 30 C at 6 PM,
How a fake typhus epidemic saved a Polish city from the Nazis
I just heard this podcast from "Disaster Podcast" that's mostly devoted to hospital sanitation. It sure raises my concern about going to a hospital for treatment. I think the emphasis was on Disaster Clean Up, so the speaker didn't didn't talk about the use of copper which would be a preventive measure, but certainly one you'd think they'd promote as a sideline. Thought the podcast might be of interest as one that connects the clinical with the research side of things.
I’m writing this email in response to episode 112. My first comment is regarding the talmudic question (which I can’t find on Small Things Considered for some reason), which generally concerned exceptions to rules in Biology. Vincent’s comment about how Taxonomy is difficult because naming conventions are based on what is currently known, reminded me of picornaviruses. When I took my first Virology class in graduate school, we learned that the name “picoRNA” is derived from Spanish, literally meaning “small RNA”. The name is based on the viral genome, which at the time was considered the smallest known RNA genome. However, since this group of viruses was named, other, much smaller RNA viruses have been discovered (such as Rous sarcoma virus, for example). Am I remembering this correctly, Vincent? Anyway, these thoughts can be further supplemented by listening to TWiV 357, which features a discussion about Taxonomy, and how imperfect this classification scheme can be. I just love how all the sciences complement each other. One can learn a lot by venturing outside one’s comfort zone!
Completely unrelated to this discussion, I would like to mention this recent article in Nature, which I found interesting.
While most antibiotics function by targeting bacterial DNA, RNA, cell wall, or protein synthesis, this potential antibiotic strategy targets a bacterial regulatory mechanism for synthesizing riboflavin. Apparently riboflavin facilitates several enzymatic reactions, which are essential for bacterial growth and reproduction. As I understand it, this is a previously unexplored strategy for development of new antibiotics. As our imminent antibiotic crisis terrifies me somewhat, I’m wondering if this something to be excited about.
Thanks again for all your entertaining and informative podcasts. They keep me thinking!
P.S. Having grown up in Romania, and having spent summers at my grandmother’s house in Transylvania, I have great memories of going mushroom picking with my grandmother, who was very knowledgeable about which ones were safe to eat and which ones weren’t. But you’re right, nobody in America seems to do this!
Mysterious fungus killing snakes in NY, at least 8 other states | wivb.com - http://wivb.com/2015/08/10/mysterious-fungus-killing-snakes-in-ny-at-least-8-other-states/
One for Elio, if he's not on to it already.
Amphibians, bats, and now snakes: have the fungi just declared war, or what?
All the best,
Thank you for your excellent discussion about graduate and postdoctoral education in TWiM 108. I enjoyed the conversation about career options for people with advanced training in microbiology. I earned my PhD in microbiology and did postdoctoral training before taking my current position as a research scientist at 3M Company. As a scientist doing research in industry, I don't think of my career path as "alternative", although I often hear that term used to describe non-tenure track careers for scientists. It would be a step in the right direction for advisors in graduate programs to start using the term "careers" instead of "alternative careers" when talking to students about options for the future. The use of the word "alternative" to describe non-tenure track career options seems to be particularly pervasive in academic departments specializing in the biological sciences. As biologists, let's start a movement to catch up to our colleagues in chemistry and physics departments where moving to non-tenure track positions after graduate school is a normal and valued option.
Many thanks for a great show. Listening to TWiM is a great way for me to stay current on a wide variety of topics in microbiology, which is not only fun but also part of my job.
I was so confused when I first heard you talking about this. It sounded so familiar I was sure you'd mentioned it before but it sounded like it was new to you. After a bit of thought I wondered if I'd heard of it during a class I took on Beowulf last spring. I checked the discussion board archive and there it was! Someone had linked to an article about it on newscientist.com. What a cool overlap between online communities! If you're still wondering, the language spoken in England back then is now either called Old English or Anglo-Saxon. Beowulf was written in that version of English and it's nearly unintelligible today unless you spend time learning the language. But there are still familiar words here and there. Chaucer wrote in Middle English which we English speakers can still understand somewhat without a whole lot of help. My favorite thing about Old English, really about pre-printing press English, is that there were dedicated letters for our "th" sounds. One was like a cross between lower case p and b which looked kind of like a mouth with a tongue sticking out. Which makes perfect sense.
Dear TWiM Hosts,
My Name is Wytamma, I am a honours student in microbiology studying in North-Eastern Australia where it feels like a pleasant 18C. FYI honours is a year of postgrad research that can bridge you into a PHD without completing a masters degree. Anyway, my question is about Taq polymerase. My girlfriend Anna is currently doing some TA cloning and I was surprised to hear that the Taq pol enzyme adds an adenine overhang to the ends of the PCR product making it perfect for this cloning method. I was wondering what biological significance this function has? I guess the the first step would be to insert a polymerase lacking this function into the bacteria and seeing what happens but I’m a little busy with my own project on ranavirus to take that on.
Thanks for the great podcasts,
All the best,
James Cook University
College of Public Health, Medical and Veterinary Sciences
[this is a property of many DNA polymerases, adding a single non-tempated nucleotide to the 3’-end of a blunt strand. Function unknown, as these polymerases copy circular DNA genomes. Perhaps it is a signal of DNA damage?]
Hi Twi Team,
Absolutely love your podcasts. I’m a public health specialist coming to the hard sciences late in life and enjoying it immensely. Thank you for all you do communicating the wonder of science.
That said… I think you blew it on the public good explanation in TWiM #111.
The reason public goods are fundamentally different than private goods is that unlike with private goods, the producer of the public good gains no advantage vis a vis his peers. If a Pseudomonas bacterium developed a mutation that allowed its siderophores to differentiate gallium from iron, that benefit would be diluted across the entire population of the colony. Everyone - including the mutant - would encounter the same environment filled with a majority of gallium-bound (and therefore toxic) siderophores. There would be no individual survival advantage to the individual that developed the mutation - thus no selection pressure.
Now if there was a mutation that allowed a cell to make use of the gallium as if it were iron in its cell processes, that would be a different story since that would be an individual advantage and would be selected for. But given the diversity of uses of iron in various metabolic pathways, the likelihood of an individual mutating to accept gallium in all the places where iron is currently used is essentially nonexistent.
So public vs. private does matter.
Keep up the amazing podcasts. My dog loves your show because he knows when I put on the headphones he’s going for a long walk!
I'm Peter, writing from Falmouth, UK (not to be confused with it's no-doubt sunnier namesake in MA). We're somewhere about 16˚C (that's about 61 in your currency), with showers, and autumn is starting to tell.
I'm just writing to comment on the evolution of resistance to public-goods based antimicrobials - the gallium storey in TWiM 111.
I'm going to first run with the assumption that there is a mutation somewhere in gene space that allows a siderophore to exclusively pick-up iron. Then the problem with public-goods (for the bacteria, that is), is that the individual bacterium that gets that mutation isn't necessarily the one that gets the fitness benefit from it: It's highly likely that the super-siderophore gets taken-up by a different bacterium, as the siderophore diffuses away from the bacteria that produced it, and then the fitness advantage is conferred on an individual who didn't have that mutation. I guess that the selective advantage for a super-siderophore will be higher in a more viscous media; one in which the siderophore remains spatially close to the bacterium that produced it.
I suppose most of the places we're going to be medically concerned about P. aeruginosa are going to be places with a bit of spatial structure, but still the fact remains that compared to a completely "privately operating" mechanism, a "public goods" based anti-microbial will be less prone to resistance, simply due to the "who gets the benefit of the mutation" idea, though it seems to me that resistance would none-the-less eventually evolve given sufficient time and selective pressure.
That's all, except I just want to say that I have a lot of love TWiM and TWiV and what you guys do; over the last 5 years of tuning-in you feel like familiar characters, the sort that I might regularly meet in the local pub and chat the night away with. And as a PhD student who never does enough reading I cannot say enough what an amazingly useful tool you guys are providing: multiple lifetimes-worth experience pouring over the latest, bleeding edge research with such wonderful insight. What an inspiration!
Cheers all, and here's looking forward to 112 and beyond!
I am writing to help clear up some confusion as to why resistance might be hard to evolve if public goods are targeted.
In episode #111, Elio talked about gallium intoxication of siderophores, and a proposal was put forth that since the siderophore is extracellular, it would be hard to evolve resistance to gallium.
Vincent said, it is the atomic mimicry of gallium and iron being so similar that is important: loss of gallium binding would almost certainly cause loss of binding to Iron.
Elio replied that both the extracellular nature and the mimicry are important, but why extracellular matters was perhaps not so clear.
I think the distinction is not extracellular vs. intracellular, but rather that the siderophore is a public good, that has impacts on a population of bacteria. In contrast, mutations that may produce an altered siderophore occur in individual bacteria.
What this means, is that mutant bacteria bacteria that produce a siderophore that distinguishes iron from gallium does not receive the full fitness benefit of that mutation. Instead, the whole population of surrounding bacteria will receive that benefit. In this manner, fitness advantages from a mutant are redistributed to a community, instead of benefiting only the mutant bacterium.
However, in my opinion, this is still not necessarily a satisfactory explanation as to why resistance would not develop. Even if the whole population receives the advantage from one individual, the mutant bacterium is among that benefited population and will receive some benefit. The counter argument would be that by spreading the fitness advantage among a population, the fitness advantage is so diluted that there is virtually no selective advantage conferred to the mutant bacterium. Personally, I think targeting public goods such as a siderophore may slow expansion of resistant alleles in a population, but not prevent them from occurring.
It's interesting to conjecture that diffusion properties of these "public goods" (to a large population or a relatively small population of bacteria) may impact the rate at which natural selection occurs.
Thanks for your great work, look forward to the next episode!
Postdoctoral Fellow Brigham and Women's Hospital
Dear Dr. Schaechter,
First off, I want to thank you for the effort you and your colleagues have invested in Small Things Considered and the podcast TWIM. Back when I had a longer commute to work, I listened more religiously than now, which is pretty much the only thing I regret about switching my job and reducing my commute. As a physicist, turned synthetic biologist, I really need an education in microbiology (that most of my peers got in graduate school), and TWIM is a great resource for people like me.
Now, a question: (I apologize if this topic has already been covered by you in a previous post or article.) Thermophilic organisms have DNA sequences that are higher in GC content in order to remain stable at higher temperatures. The enzymes and protein structures found in thermophiles are also significantly more thermostable. If you were to examine a conserved enzyme from psychrophile through the temperate zone and up to thermophile, what do you see in terms of its amino acid content? Are there certain amino acids that are correlated with thermodynamic stability of the protein (fold)? Do these amino acids correlate with higher GC codons? If so, do you believe that this was part of the driving force for the evolution of the genetic code? Namely, that a more thermostable codon should correspond to an amino acid that is more likely to contribute to a more thermostable folded protein. (This thought never occurred to me before, but I read the abstract of this paper (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC403753/) and it seemed to imply this concept, which struck me as sensible, but I hadn't heard it before.)
Thanks, in advance, for any thoughts and for your time to help educate us all,
Christoph Weigel responds:
in principle, your ideas are fine. yes, GC-rich DNA has higher melting temps., GC-rich genomes - as e.g. streptomycetes - tend to have a bias towards G and C at the 3rd position of codons in their genes, and also more G and C in conserved transcription factor binding sites. however, there's a big caveat: one of the most thermophilic bugs we know today,
the archaeon pyrococcus furiosus (grows at 100°C, has a wikipedia entry), has a genomic GC-content of 40% (see here: http://www2.unil.ch/comparativegenometrics/AE009950.htm) that's 10 points less than e. coli. if i remember correctly, there is evidence that this bug employs histone-like proteins to keep its DNA double-stranded. and given it's low genomic GC-content it can't have this codon bias. i could/would go into more detail - if you want - but not before end of september as i'm on vacation right now, enjoying açores islands :)
then Noah responded:
Hi, and thank you for your quick response from your vacation. (Do not feel that you have to respond again before returning!)
I guess my question was not "do all microbes that live at higher temperatures also have higher GC-content genomes?" since that is easy to disprove, as you pointed out... Instead, I am wondering about the evolution of the genetic code and the transition from a RNA-world to a protein-world: At this moment in evolutionary history, was thermodynamic stability a driving force of the genetic code? I am assuming that an early RNA-only ancestor of modern life (all of which has protein enzymes, correct?) would very likely have needed ribozymes that were stable at its ambient temperature, and thus, higher in GC content. Also, we should be able to determine (using bioinformatics) if microorganisms that survive at higher temperatures have a consistent skew in the amino acid content of their proteins. For example, if these thermophiles had a disproportionate number of Gly (GGN), Ala (GCN), Pro (CCN), Arg (CGN), then you might be curious about whether thermodynamics were a factor. Looking a little more deeply, you could also ask whether individual transitions from similar amino acids (such as Lys to Arg) contribute to stable folds, since they are also more stable codons (e.g. a comparison between AAA and AGA).
I think it's probably clear that this will not account for everything, but just wondering whether anyone else had thought it may have been a factor. Are there any papers considered "seminal" in the field of the evolution of the genetic code?
Thanks again for your time! Cheers and enjoy the rest of the summer!
I was quite excited by your podcast on AMPs since I studied bacteriocin usage in bacterial vaginosis (BV) prophylaxis as part of masters. So in response, bacteriocins have been identified that inhibit BV-associated pathogens while having little impact on normal microflora in laboratory environments. There's been some promising research on bacteriocin usage but it's been most extensive in food research. Finally, a self plug for a recent publication: I just wrote a review on bacteriocins and their potential usage in conjunction with antibiotics which is currently in press in IJAA.
I love the podcast so much!
Have you seen this? Unbelievable!
It is 64F and "rainless" in Seattle.
Love the podcasts.
Love the podcasts, keep them coming! In response to Michele bringing up the NYC Legionella outbreak Vincent was trying to come up with Michigan-specific infections. Unfortunately, here in Southeast Michigan (mostly in Detroit) we seem to have created a breeding ground for infections with highly resistant organisms including CRE, VRSA, healthcare-associated Acinetobacter, and even a "small" outbreak of 5 cases of colistin-resistant, carbapenem-restistant Klebsiella. (http://aac.asm.org/content/55/2/593). Some have suggested this is due to the high prevalence of diabetes, end-stage renal disease, as well as high baseline rates of MRSA and VRE infections in the area. All of these factors increase the probability that a patient will at some point require vancomycin or a carbapenem to treat an infection. So apparently multidrug-resistant organisms are Michigan's microbial gifts to the world. Anyway, as a medical student I don't get a ton of time to enjoy our wonder summer weather (27°C today) so I'm going to go do that while it lasts.
Pages 41 to 45 of Popular Science magazine, Aug 2015 discusses the danger of our war on bacteria and viruses. They cite hospitals problems where 75000 people die of hospital acquired infections in spite of strong efforts to make things sterile. This war may be related to the rise of the superbug that is rendering our antibiotics useless. The space Station is probably a dangerous place because of the lack of normal microbes.
This article in the most recent issue of Scientific American (special issue with a picture of Einstein on the cover) reminded me of the points you raised during a recent episode of TWiM.
It has long been my opinion that the best advice to give to someone in school is to develop expertise in two complementary fields. In my case I was able to combine skills in shipboard engineering and maintenance with at least a modicum of understanding of computer technology. Similarly, I think that someone with a degree in microbiology who is fluent in Portuguese (the Brazilian variant) or Chinese would be in a strong position. A person with a degree in microbiology who went to law school and specialized in intellectual property law could probably retire at 40.
The attached article describes a need for a marriage between computer scientists and neuroscientists (and by extension with any of the biological sciences). That marriage sounds like a promising “combination” for a student — a major in microbiology and a minor in computer science, or vice versa.