PCR AND A DANCE IN THE MIND FIELD

PCR stands for “Polymerase Chain Reaction”, but it could just as well be “Polymerase Chain Revolution”.  I know that even those who do not work on DNA or molecular biology are aware that PCR is a tremendously powerful tool that influences many areas of our life.  Forensics is a classic example, when PCR is used not only to help a prosecutor’s case, but what I find even more fascinating, to prevent innocent people from paying for a crime they did not commit. Many people on death row have been released from prison thanks to one of the most elegant and surprisingly simple techniques in molecular biology. Through PCR, a specific segment of DNA is replicated over and over and over inside a tiny plastic tube. The ability to make a lot of DNA starting with a few molecules opened the doors to countless types of studies, from evolution to detection of genetic and infectious diseases. For biochemists, it is actually impossible to do research without PCR.  Taking our lab as an example, we use it almost on a daily basis, either to make precise alterations in bacterial genes, or to delete bacterial genes from the chromosome.  Without this technology, many of our experiments could not be performed, whereas others would take months instead of days, or even hours.

The genius behind the invention of PCR is Dr. Kary Mullis, who won the Chemistry Nobel Prize exactly twenty years ago, in 1993.  His own recollection of his scientific journey can be found in the fascinating (and at times controversial) book “Dancing Naked in the Mind Field”.

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“We were at mile marker 46.58 on Highway 128, and we were at the very edge of the dawn of the age of PCR. I could feel it”. (Dancing Naked in the Mind Field, page 7)

Phil and I happened to travel right through that highway several times last week, and we made sure to take the book with us so we could read it under the spell of that beautiful setting.

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“When you  get the hang of it, science, like everything else people do for a living, is pretty straightforward. You are in the business of solving puzzles. The way to approach a puzzle is to think about it for a while, look at all the facts you can find out about it, and then take a guess.  Propose a solution. The next step is to try your best to disprove your solution. Show that the pieces don’t fit together in the way  that you have proposed. If you can do that, then propose another solution.  And then do the same thing. Reality is a tricky little puzzle”.  (K. Mullis, Dancing Naked in the Mind Field, page 50).

Through my work, I had the chance to meet incredibly impressive people.  One such person was Joe Neilands, Phil’s PhD advisor from Berkeley.  The impact of Neilands on Phil’s scientific career and political views was huge. Even though Joe passed away many years ago, Phil always includes a picture of him in his talks, a well-deserved tribute to the man who discovered siderophores.  Siderophores (as I mentioned in the blog before)  are molecules that allow bacteria and other microorganisms to survive in a world where iron is virtually unavailable.   I knew that Kary Mullis was a PhD student in Neilands’ lab, in fact he was still around for a while when Phil joined the lab. I was thrilled to find out several references to his great mentor in the book.

“The lab in which I learned the most about life was presided over by Joe Neilands. (…) Joe Neilands made me aware of the present-day planet.  I already knew about the universe but had spent little time thinking about today and the people around me”. (Dancing Naked in the Mind Field, page 35).

Tomorrow will be a special day for us.  Kary Mullis will be in town to present a conference at our department, invited by Phil.  He will have lunch with graduate students, talk to faculty, and certainly fascinate us with his recollections of the discovery of PCR.   The talk is open to the public, so if you find yourself “in the neighborhood”, consider dropping by…    😉

NOTE ADDED AFTER PUBLICATION OF THIS POST:  Conference will be streamed live and open to the public, so if you want to listen to him, join us by clicking here (you can also watch it later, it will be saved on the site).

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I am so excited to finally meet him! I know it will be a great event for our department and a unique opportunity for graduate students to interact with someone who is not only brilliant, but is also not afraid to speak his own mind and to swim against the current, no matter how strong a current it is.

“The laws of science are demonstrable. They are not beliefs. When experiments in our century showed that Newton’s gravitational laws were not quite accurate, we changed the laws – despite Newton’s good name and holy grave in Cambridge. Relativity fits the facts better. This  is the way science has been done now for almost four centuries, and because of science – not religion or politics – even people like you and me can have possessions that only a hundred years ago kings would have gone to war to own. Scientific method should not be taken lightly”.  (Dancing Naked in the Mind Field, page 112).

ONE YEAR AGO: October 16: World Bread Day

TWO YEARS AGO: The US Listeria Outbreak 2011

THREE YEARS AGO: 36 Hour Sourdough Baguettes

FOUR YEARS AGO: October 16 is World Bread Day

31 thoughts on “PCR AND A DANCE IN THE MIND FIELD

  1. I bet it’s going to be exciting for your undergrads and graduate students to have such an eminent researcher at your univesity. I wish I were in town just to enjoy the excitement of being in the same room as a Nobel laureate. 🙂

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    • I am definitely looking forward to it – my experience meeting Nobel laureates has been “interesting” to say the least. In one case (I shall never name names ever!) I could not wait to be away from the man. Toxic personality. But it was a sorry exception to a rule of great interactions!

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  2. I stopped by this morning primarily because I’m an egocentric narcissist (is that redundant?) and needed to brag about how well I made your Brazilian queso/cornmeal/futbol cake in my rice cooker – again. And then I was going to continue my self-congratulatory spree by shining a hot white spotlight of attention towards my blog, where I showcase a baked apple stuffed with apple pie thingy I came up with, and now serve to riotous applause.

    But now that I’m here….I’ve gotta have that book! Just like you, I’d devour every page. Unlike you, though, I wouldn’t understand it. But that’s ok – as long as I can tell my friends I read it, they’ll be impressed. And that’s what counts.

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    • I would bet you would love the book and understand every bit of it… Mullis comes across as a great teacher. His explanation of “Avogadro’s number” is the clearest I’ve ever read, and a 5 year old kid would get it. An important concept in chemistry, that leaves many students hanging 😉

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      • OK, I better read it too. I’m taking an online course, https://www.edx.org/course/harvard-university/spu27x/science-cooking-haute-cuisine/639, on the science of cooking. It’s a bit more rigorous than I expected. My current homework assignment involves computing the difference in the number of gluten molecules in a cup of flour when volume is used in a recipe instead of weight. I know I could have done this easily 40 years ago but now I’m struggling! Do you or Phil have time to do some tutoring? For now, I’m trying to stick with the course. I’m only auditing so I can withdraw without consequence but I prefer to finish what I start, if possible. I did a fun lab yesterday – documented that my oven and 2 thermometers I use are properly calibrated, at least in the temperature range at which sugar melts (366F).

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        • Cindy, the number of molecules of gluten would be tricky to measure – gluten, as you learned, is not a uniform molecule, but a polymer formed by two kinds of proteins, one of them is water soluble, the other is not. Because of the polymeric AND VARIABLE structure (no regular proportion between the two proteins), calculating the number of molecules in a given amount of flour is dicey to say the least. The only way to do it is to assume an average molecular weight for it and go from there, which I suspect it is what they will give you: a starting value as the molecular weight for gluten. Since in this exercise their goal is to demonstrate the difference between measuring in volume or in weight, no major harm done. But you should keep in mind that the numbers you obtain for each condition will likely not be the real number. Because both conditions involve the same type of flour, the error in both measurements will be the same. Bottom line, the exercise is doable and will give you nice info, but deep inside, there are flaws… 😉

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          • We are given links to the references we will need. One will include the density of flour. I’m starting to think this assignment is not a good use of my time. Relearning chemistry at this level will not likely make future endeavors more successful or enjoyable. Since I am auditing the course I can watch the lectures without participating in the graded exercises. I found the lecture associated with this assignment interesting, particularly comparing the number of molecules of each of the ingredients in a cookie recipe. I have a better understanding of why precision in measuring can be so important in baking. If I don’t do the assignment it will be the first time in my life I didn’t hand in a homework assignment. I know this sounds silly but that bothers me! Justifying myself now; I just found out I am having guests for dinner on Sunday. Wednesday (today) is the best day to shop in the city. For my guests I’m going to try to recreate the best meal of my recent driving tour of the south – Saw’s pork and greens. Given my current life-stage I think this is more important than relearning how to use Avogadro’s number. I will accept that my days of scholastic achievement are over and be grateful that I can use my time in the ways that bring me the most pleasure.

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  3. Ah, the Father of PCR, what an honour to have Dr. Mullis speaking at your department tomorrow — I’d be particularly interested in hearing his views on parapsychology 😉 and I’ve always believed that light can be switched on by thought. The fact that I would be terrified if I ever managed to make it happen acts as an absolute barrier me thinks. Everything is energy. Have a great day Sally.

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    • I can see you either read his book or heard of his experiences with skin resistance & thought control…
      Pretty fascinating stuff, but there’s a lot more in the book that might surprise the hard core scientists – like his views on astrology, HIV, and I must say nutrition 😉

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  4. When I clicked on your blog I certainly did not expect to share your pleasure at Dr Mullis’ visit at your Uni nor have such an interesting link to a possible learning experience for myself. My uni biochemistry studies lasted but a year in Medical School quite some time ago, but it would be a fascinating challenge to see exactly how much sense I could make of Dr Mullis’ book!! Hope you had a wonderfully fulfilling time.

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    • well, we arrived back from the business trip on Sunday at 1am, had Monday to try to recover, even though it was a normal work day, and now it is this amazing event that we are hosting, or I should say Phil is hosting, I am just a tiny supporting role… 😉

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      • Don’t underestimate your contributions. As his partner you are most certainly responsible for some of Phil’s success. I bet he would be the first to acknowledge that he wouldn’t be where he is now if you had not been along for the journey.

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  5. I loved the quote about science being a matter of solving puzzles.What I love the most about being an orthodontist is that every case is a puzzle and you have to put it together. Sure it is not the same as cutting edge research but still, this is what I love about science 🙂
    I wish I was “in the neighborhood”, I would love to attend such a talk!

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    • One of my favorite quotes of the book indeed – I feel exactly the same way with our work, although solving some parts of this huge puzzle seem like a daunting task 😉

      Too bad you were not in the neighborhood, I sent you the link by email, but maybe the time difference made it impossible for you to watch it

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  6. Amazing!! Wow, I wish I could be there! it really is awesome to meet some of those “greats”. I’ve gotten to meet a few of them between Cornell/the Rockefeller/and Sloan-Kettering and MIT it is always crazy to hear them speak, especially when they are just humble normal people (as opposed to some of the more arrogant individuals you sometimes encounter). And yeah. I couldn’t live without PCR.

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    • You said it all….

      well, his visit is over, and life slowly goes back to normal. Although I must say “normal” in our life is far from uneventful… it seems we have one thing after another, over and over and over, like a crazy endless PCR 😉

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    • Celia, what a great experience it was! It is always a bit nerve-wrecking to be part of such an event – things can go wrong on so many levels! It is good to have this page turned without a flaw! Very proud of Phil and his staff.

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