S04E10: The Alien Parasite Hypothesis

Tonight Amy prepared a brain sample for her two-photon microscope.  A two-photon microscope works on a principle that violates the basic statement of Einstein’s work that won him the Nobel Prize.

Amy Farrah Fowler prepares samples for her "two-photon microscope".

Amy Farrah Fowler prepares samples for her "two-photon microscope".


Einstein was busy in 1905,  often called his Annus Mirabilis (his “Miracle Year”).    He produced his work on special relativity– but he never won a Nobel Prize for that.   He produced the linchpin  for an elementary explanation for thermodynamics–but never won a Nobel Prize for that either.   Einstein’s Nobel-Prize winning work that year explained the most basic interaction of atoms with light, and forever changed our view of light.

Atoms are made of two charged particles, protons and electrons.  Through those electric charges they interact with light.  Modern physics has been studying these interactions for over 100 years and is the basis of everything from lasers to making pornographic pictures in airports backscatter X-ray scanners at airports.  Einstein’s Nobel Prize explained how only light above a certain energy will free an electron from atom:  Giving a small amount of energy to an electron in an atom may wiggle its orbit a bit, but won’t break it free.  Only with a large enough kick can an electron be separated from its atom.  But physicists found that visible light, no matter how bright, would not knock electrons free from a material, while even a weak ultraviolet light could.

Einstein proposed a solution.   He predicted that the energy of a beam of light was carried by individual particles of light, now called photons.  He  borrowed the idea from Max Planck, who had assumed such quantization  to explain the color and brightness of hot objects.    But now Einstein took the idea not just as a mathematical trick, but as a real description of the nature of a beam of light.  So light would collide with atoms like two billiard balls.  For most materials, visible light particles do not carry enough energy to knock electrons out of atoms.   Only ultra-violet light has enough energyto knock out electrons.  No matter how intense you make a the visible light, the story goes, you will never knock out electrons because the individual photons do not have enough energy. Because this represents one of the most basic interactions of light (the photons) with electrons is called the photoelectric effect.

During my own undergraduate days we demonstrated this effect in our student laboratory.   We shone light onto a metal and looked for a charge buildup due to escaping electrons, just as it would if it were exposed to static electricity.    But no matter how intense the visible light, no charge was built up.  But a small ultraviolet lamp, such as you might use in a tanning bed, quickly charged the metal.   Only ultraviolet photons have enough energy to knock out electrons, so there is a minimum for anything to happen.   This is the same reason that rays damage your skin so easily, but visible light does not.

“Wait!” you might be thinking.  What if the atom could absorb two particles of light, “two-photons”, at once?  Couldn’t the combined energy of two low-energy, even infrared photons, be enough to kick out an electron?   And you’d be both right and eighty years too late.  The effect was predicted by Maria Goeppert-Mayer in her 1931 Ph.D thesis.   She later went on to win a Nobel Prize of her own for completely different work, explaining the structure of the atomic nucleus.

In her 1931 Ph.D. thesis, Maria Goeppert-Mayer discovered an effect Einstein missed: two-photon absorption. This became the basis of the two-photon microscope.

The effect is very small, since two photons must combine with the atom at the same time.   Most collisions of light with atoms are so small they are characterized by a small area.   In my undergraduate lab we did not have anywhere close to the intensity for this effect to even begin.  The effect predicted by Maria Goeppert-Mayer was so small that a new unit of measure, using the square of the small area,  had to be invented.  To this day, the unit is called the “GM” in her honor.

The effect would have remained just theory, without a light source intense enough to produce it experimentally.   Charles Townes, the inventor of the laser, had such a device.  His student, Isaac Abella (later one of my professors) was one of the first to demonstrate two-photon absorption experimentally, using infrared laser light to produce absorption at a factor of two less energy than Einstein’s model.

The two-photon technique has revolutionized the ability of scientists (and if I were  Sheldon I might add  “…and biologists”) to study thick biological and even living tissue.  A two-photon microscope uses precisely this effect predicted by Goeppert-Mayer.     Hence the discussion:  Sheldon complained to Amy she was cutting the samples to thin.  You can’t slice tissue too thin for an electron microscope, but thick samples is where a two-photon microscope comes into its own.   Lucky for us, Newport Corporation lent us a two-photon microscope, the one you see on the show.

In a two-photon microscope, not enough energy is delivered to liberate the electron, but does excite the molecules of a flourescent dye with two photons.  The resultant single photon fluorescence is a single photon of nearly twice the frequency of the incident red or infrared light, typically green and can be separated from intense incident light to form an image.

An image taken with a two-photon microscope of a neuron from the brain of a mouse. (Journal of Neuroscience)

Another advantage is that the rate of exication now depends on the square of the illumination, since the technique needs two photons to be absorbed.  By carefully focusing the incident light, only one small selected region of the sample glows, allowing a detailed picture without the extraneous light from everywhere else, as you would have in a conventional microscope.

And so we finally see scientists wearing lab coats on The Big Bang Theory.  That’s what happens when you let in the biologists.

16 Responses to “S04E10: The Alien Parasite Hypothesis”

  1. Chaitanya Says:

    LOL @ the strike through

  2. tudza Says:

    You would think of all people, these two would follow the “Don’t eat or drink in the lab” rule, especially when one of them is preparing samples.

  3. chimpanzee Says:

    I was at 2010 CES (Consumer Electronics Show) as part of my STEM (Science Technology Engineering Mathematics) Outreach project. Canon had an interesting booth, which portrayed Scientists doing “cool science”:


    It looked like a chemistry lab, with colorful liquids & experiments (incl “growing sand”). Very entertaining. Actors (the guy was a math teacher in the Las Vegas area) donning labcoats. They threw in a solar-system model (“Astronomy/Astrophysics”) & human-foot model (“Biology”), to make the set have broad appeal.

    A) Information
    real Science

    B) Entertainment
    fluff: actors, colorful liquids, wowie-zowie demos, mixing Astronomy/Biology/Chemistry

    “A” is too boring, the Public won’t get inspired. A+B will pull it off. Your role is to have enough “A”, without “B” making it ridiculous.

    “There are many many people who strived for a career as a concert pianist [ scientist, Racer, etc ] ahh..the Ones that SUCCEED..just accept the fact that they have fabulous technique..and accept the fact, you know, they can play the instrument..WHAT makes people SUCCEED, is how they are able to CAPTURE THE AUDIENCE
    — Schuyler Chapin/Impresario, “The Art of Piano”

    Classical Piano (& Classical Music in general) are niche-markets like Science, who have the problem of attracting a “mass-market” audience. Franz Liszt invented the “piano recital”, to do Public Outreach (what was once a very private affair amongst composers). Modern day classical artists (pianists & violinists), are further developing the Concept. Using Technology like Youtube. Lang Lang (Chinese pianist, controversial like L. Motl for his public personna) has hit the big-time: he has 9 (?) full-time Public Relations staff, to push his “brand-name”. He has sponsorship from Audi, Adidas (special signature shoe), Rolex, et al.

    “What sets Artur & Okasana apart [ from their competition ], is that they used the Technical Elements [ particle physics ] to TELL A STORY [ Big Bang Theory ].”
    — commentator, Youtube video: Dmitriev/Kazakova, 1998 Olympics pairs gala

    Figure Skating (sport) has “captured the audience”, & created a huge brand-name for Olympics & Professional Circuit. Complete with sponsorship.

    The above 2 markets (“Art”) have an easier path to seduce an audience. Music Dance don’t require explaining.

    “You don’t need brains to appreciate Music”
    — L. Pavarotti

    Science appeals to the Intellect, which is a tough sell. Especially, given poor STEM (Science Technology Engineering Mathematics) awareness by US Public.

    “There is a recognition that there is a science illiteracy in the country. They are very internet literate but we are not tapping into this directly. We have too little effort going toward education and student involvement. Money doesn’t always go towards training students. A major US problem is that we have a very high level of scientific accomplishment and meager science literacy in the public.
    — Steve Lord, Caltech/IPAC, Astro2010 Town Meeting (Re: 2010-2020 Decadal Survey)

    I heard that the Sheldon Cooper character was based on L. Motl (a real character), but never watched BBT. I happened to catch an episode last week, & last night. It’s really good, the acting & Science talk is right on. I became a fan.

    “It’s the 2nd rated sitcom, pulling in 12 million viewers per week”

    At the same 2010 CES, I attended Supersessions (e.g., Hollywood Creative Masters: A Media Money Makers SuperSession) & queried many Hollywood people on the “STEM Outreach” problem. 1 guy I asked immediately quipped:

    “make it funny [ comedy ]”

    At the time, I thought it was dumb. Now, given the success of BBT (& Emmy Award to Jim Parsons), he is right. Americans are science-illiterate (“Dumbing Down of America”, a favorite quote by a geologist friend of mine), & the only way to connect with them is thru their funny-bone.

    I think BBT will have a spinoff effects (just like Apollo space program created New Technologies, like integrated circuit, etc), & there will be more related TV/Movie content. L. Motl will probably have a future like Lang Lang, a very marketable brand-name.

  4. jimhong Says:

    You studied under Isaac Abella? Did you attend the University of Chicago? I knew Dr. Abella there, though I did not take a class from him. While I was in the Dept. of Chemistry, the way I knew him was that he was the resident master of the dorm I happened to be president of at the time.

  5. feldfrei Says:

    Thank’s again for another enlightening TBBT blog. Einstein’s work on the photo effect was quite intuitive and forward-looking since it turned out later that for “photons” one needs to quantize the radiation field (so-called “second quantization”). Solving the time-dependent Schrödinger equation for an atom interacting with classical electromagnetic waves (i. e. light) one gets out the photoelectric effect automatically due to interference of periodically outgoing electronic wavelets (with photons being introduced nowhere in this case). Even the “multiphoton ionization” (according to Goeppert-Mayer) shows up if the intensity of the light field is sufficiently large.

    Thanks for mentioning C. Townes. There has been much debate in the literature about the first working laser. Usually one finds that T. Maiman built the first laser in 1960. However, from today’s viewpoint Maiman’s first ruby laser set-up was not a working laser as discussed by A. Lauberau (What is a Working Laser?): http://www.aps.org/publications/apsnews/200405/letters.cfm
    According to this article, the first working laser was built by R. J. Collins.

    P.S.: I like Sheldon’s explanation why 73 is the “best number” and wrote a short comment on that: http://feldfrei.wordpress.com/2010/12/12/73-the-best-number/

  6. feldfrei Says:

    Just want to report the breaking news: TBBT and Jim Parsons were nominated for the Golden Globe!
    Congratulations to Jim and the cast, crew, writers and producers and last but not least to the scientific advisor David Saltzberg!

    All the best also on behalf of the TBBT fans at MPIK Heidelberg,
    Bernold Feuerstein

  7. Virginia Says:

    I resent the “anti-biologist” jokes, but still can´t stop watching the show or, now that I’ve found it, reading this blog! Congratulations on both!

  8. Top 5 Things I Learnt This Week… » New Sense Says:

    […] A two-photon microscope works on a principle that violates the basic statement of Einstein’s work that won him the Nobel Prize. (Another beauty thanks to The Big Bang Theory) – More Info […]

  9. Oddny Says:

    Hi there,

    As the major science influence behind this great, great show, could you do me a huge favor? Try to influence the incorrect understanding the writers have about lactose intolerance. As a scientis myself, although in genetics, I cringe every time Leonard has cheese and gets “affected”.

    Lactose is digested with the aid of an enzyme that is lacking in lactose intolerant people. There it simply ferments in the lower intestents. This form of sugar is however only present in milk or at worst yogurt. It isn’t present in cream, butter or cheese. There it’s already been fermented and poses therefore no threat to those unfortunate lactose intolerants who eat it.

    I know this is nit picking at it’s worst but everything else about the show is just so well constructed that I wish this would be changed! Even at the cost of a few flatchulence jokes…

    Keep up the amazing work! I look forward to seeing the Big Bang theory every week.

    • David Saltzberg Says:

      That’s very interesting, thanks. I’m not an expert but according to Wikipedia: “Commercial cheese brands, however, are generally manufactured by modern processes that do not have the same lactose reducing properties [as aged cheese]” I don’t ever want to stand in the way of a flatulence joke.

      • tudza Says:

        Very noble. Ever man, woman, and child must do his fart, uh, part.

        Think I’ll check out the Kraft website on this one, just for completeness.

      • Oddny Says:

        Oh agreed! However, should poor Leonard not be able to enjoy cheese on his pizza?Let’s face it, by then all the residual lactose in that cheese should by then be completely fermented, if it is real cheese to begin with…. Although Wikipedia has been an awesome source of facts for me I still maintain that Lactose intolerance is one of those misunderstood subjects prone to reductionst theories. Now I’m not a clinitian, and my work is in the evolutionary sector, on really old dead guys but my studies of lactose Tolerance have led me to this conclusion.

        BTW – so glad I’ve found your blog. Will immerse myself in physics, just hope you’ve dummed it down enough for me!

  10. tudza Says:

    Here is what the fine folks at Kraft have to say:


    I doubt that the Kraft product with powdered cheese is any use since you add milk to it. The Deluxe brand with the pre-mixed cheese that I prefer to use on the now rare occasions I crave the stuff lists 3g for the sugar/lactose content.


    Probably safe for many, but I’ll go with David on this one and say Leonard is on the sensitive end of the scale “For Comedy!”

  11. Carla Says:

    I have noticed that recent episodes of Big Bang Theory have been seriously lacking in scientific theorems and references. In fact it seems it’s been 12 episodes since your last post about an episode in the show. I really miss the scientific aspects of the show that made it feel educational AND entertaining. Especially coming back to read your amazing blog elaborating on the references. So please please make more!!

    Also I was wondering if you had any influence on the set. When watching the show, I see Leonard and Sheldon have several scientific volumes on their bookshelves behind the couch. I was wondering if you could tell me what some of them are? Thank you!!!

    • David Saltzberg Says:

      Thank you for the kind words. I have always able to find science in all the episodes so far. After all, physics is everywhere. I’ve not been posting lately because my research has had me too busy to find the time to write. I will make entries for the final 4 episodes sometime over the summer.

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