FIVE MINUTES IN L.I.T.

L.I.T., you ask? Well, that stands for Laboratory of Iron Transport, and it’s where I spend most of my waking hours. In brief, we study how bacteria such as Escherichia coli and Listeria monocytogenes get iron from the environment and “swallow it up.” The metal is indispensable for bacteria as well as all other living organisms to survive, but it is very tricky to obtain. Iron can be compared to money in the sense that everyone who has it tries to protect it from being taken away. However, bacteria developed sophisticated systems to do just that: steal the iron from you and use it to survive. Since all pathogenic bacteria need to obtain iron to cause disease, we hope that our research will lead to the discovery of new weapons to fight infections.

We thought – actually, let me give full credit to Phil for that – he thought it would be fun to walk through the lab and ask what each person was doing, in an informal and fun way.  Unfortunately, two of our undergrad students were not available when the video was made: Noah Long and Dallas Hyder. It was tricky enough to get everyone else there at the same time. I think the video turned out pretty good, as it was totally improvised.

Check it out here.

It makes me very sad to see Brittany Nairn, our super star Research Professor, getting ready to leave our group. She is the person who shows up in the video once Phil goes through a closed-door to our darkened “Fluorescence Spectroscopy Room.” We wish she could stay longer as a member of our team, but unfortunately that’s not possible.    She will go on to write her own story, and we know she will be successful and happy no matter the path life takes her. Our whole lab will miss her terribly…

CREDITS IN ORDER OF APPEARANCE

Yan Shipelskiy – Graduate student working super hard to develop a full system of evaluation of iron uptake in Gram-positive bacteria

Olivia Eliasson – Undergrad student working with Dr. Nairn to evaluate compounds with anti-bacterial activity linked to blocking of iron uptake

Dr. Somnath Chakravorty – Post-doc who recently joined our lab, working on iron uptake genes from Klebsiella pneumoniae

Aritri Majumdar – Graduate student performing very tricky experiments to evaluate the effect of bacterial membrane integrity on iron uptake

Ashish Somvanshi – Graduate student who just joined our lab, also working on iron uptake by Klebsiella pneumoniae

Dr. Brittany Nairn – Research Professor who joined our lab in August last year, and developed from scratch a whole system to evaluate iron uptake in a pathogen called Acinetobacter baumannii

Dr. Sally Newton – yours truly, molecular biologist by day, food blogger by night. Performing her favorite type of experiment using radioactive iron. Because, you know… some like it hot!

Director, Producer and Narrator,  Dr. Phillip Klebba… My favorite scientist in the whole wide world!

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Our undergrad student Noah Long, missing from the video, but proudly showing the results of his labor: the best batch of enterobactin ever purified in our lab!  How cool is that look?

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Before I leave, I invite you to watch this video of Dr. Phil Klebba explaining in more detail the research of our group. Sorry, ladies, he is already taken.

 

 

 

VENTING ON VACCINES

Disclaimer #1:  This is not a food-related post

Disclaimer #2: I am taking my gloves off

Few things upset me more than the disturbing movement to stop vaccinating babies and kids. For a while now I’ve been debating whether I should write about it. Having watched an episode of Frontline the other day that dealt with the subject, and almost succumbing to cardiac arrest while screaming at the screen, I decided I cannot stay silent any longer. First of all, let me get this straight out up front: I have a doctoral degree in Biochemistry, three years post-doctoral experience in the Department of Microbiology and Immunology at Stanford, and I taught Microbiology to Medical students in Brazil at Universidade de Sao Paulo. I also worked for about 10 years on basic research into the biotechnology of vaccines.   I’m not bragging, but I am stating my experience, that hopefully will convince you to read what I want to say,  especially if you are part of the non-vaccination crowd.  And, by the way, if you are part of this group YOU ARE WRONG. There is no equivocation or debate on this point: the truth is not subject to a democratic process.  It’s not a matter of opinion, personal choice or civil liberties. It’s a matter of what is right versus what is wrong. What is responsible versus what is reckless.  The anti-vaccine position cannot be intellectually or ethically justified, and it is morally wrong.  When the health of children is at stake, then morality becomes an issue.

I don’t criticize anyone for ignorance of a topic (and this is a complicated topic), but a parent doesn’t have the right to put the lives of their, or anyone else’s children at risk because of their ignorance.  If you are anti-vaccine, then you are ignoring over 100 years of research on immunology and microbiology.   I am not going to mince words here, because this is a subject that is too serious to mince words:  the anti-vaccine movement is socially irresponsible.  Anti-vaccine advocates deny both the mortal risk of bacterial or viral infections, and by their actions they potentially commit a crime: the crime of resurrecting horrible diseases that would otherwise, and should otherwise,  stay as nightmares of the past.

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Measles cases from 2001 through 2015: from this source

 

If you watch the Frontline episode you’ll become acquainted with a young mother from Ashland, OR, who is clueless about microbiology and immunology.  This woman, who has a doctorate in English, was so mistaken in her arguments that it shocked me that the producers devoted more than a few minutes to her reasoning. I will use her “arguments” to highlight the crucial points of this discussion.  I’m quoting from memory, because I can’t bring myself to watch the show again, but even if the words are not exactly what she said, I  preserved the gist.  You can trust me on that point, and you can watch the show if you’d like to double check it.

“Why are we vaccinating kids today with so many vaccines, when previous generations had fewer vaccines and they were ok?” Oh, dear…  I could answer that with three simple words: BECAUSE WE CAN. Because more vaccines became available over the past two generations.  Because we should immunize with even more vaccines as they become available. Because no one born in this country after the 80’s should risk contracting measles. Or mumps. No one born after the 60’s should contract poliomyelitis, tetanus, or diptheria; no one born after the 80’s must face bacterial meningitis.  Or any other infectious disease for which a vaccine is available.

“Why would I vaccinate my young girl against a sexually transmitted disease (Human Papilloma Virus, HPV) when obviously she’s not sexually active and won’t be for many years?” Oh, dear…  If you bothered to study Immunology 101, a subject that you are so quick to misrepresent, you would learn that immunity begins during the first encounter with a pathogen (or its selected components), but must be reinforced (boosted) by subsequent encounters, which explains why some vaccines are repeated over   months or years. It’s all part of generating special cells called “memory B-cells” that stay in the bloodstream in very low numbers, awaiting another encounter with the specific pathogen (or in this case a small part of the pathogen, loosely defined as an “antigen”) to show up. Once in contact with the pathogen again, memory B cells  proliferate and generate a huge quantity of neutralizing antibodies that will prevent you from becoming sick.  Another, more complex “arm” of the immune response, “cellular immunity,” also plays a role in protection against infection, but let’s not get too technical.  Different vaccines promote immunity for different amounts of time, and require different doses and boosting schedules. In the case of the HPV vaccine,  preteens develop a stronger response than teens and young adults, and for HPV vaccines to take effect they must be given prior to exposure to the virus.  That’s why doctors recommend vaccinating young kids, as early as 9 years-old.  They do not imply that your daughter could be having sex at age 9. It’s all about optimization of immunity.  And let’s not forget that infections with HPV lead to higher rates of cervical and ovarian cancer later in life, so the vaccine has a purpose and  a positive effect on human health.

EPPUR SI MUOVE
(Galileo Galilei, 1663)

“Why do we need to vaccinate against polio? There is no more polio around!”  The expression on her face was one of “I am so clever, see how I gotcha with that?” You know what her remark made me think of? Someone who might have asked 200 years ago: “…is the Earth moving around the sun? Of course it’s  not!  I would feel it moving if it moved. I am so clever, see how I gotcha with that?”  The reason we do not see polio in the US anymore is simple: comprehensive vaccination reduced the number of people who may contract the virus and spread it.  Is a vaccine 100% efficient? No, such vaccines don’t exist because the complexities of each individual immune system may prevent some people from responding to a particular vaccine.  If a small fraction of the population is not protected, it’s usually OK, even when the virus is around, and chances are no one will get sick.  So, if someone comes to New York from Pakistan (where polio is still endemic), bringing with him/her the virus in an airplane,  and walks around in the city for a couple of weeks, it’s likely that no one will contract the disease because the vaccination campaign started in the 1960’s provided solid immunity to almost all New Yorkers.   Now, suppose instead that the person lands in Portland, OR,  and travels to the Shakespeare Festival in Ashland, OR, where the percentage of un-vaccinated individuals is much higher. In Ashland a bunch of people (full of good intentions, but clueless about the relationship between immunology and health) are busy waving flags and demanding that their kids be spared from dictatorial, mandatory vaccinations. You will have a much, much higher chance that some innocent un-vaccinated child  will contract polio in Ashland.  And because many kids are not immunized in that community, it could mark the beginning of a polio outbreak.   For heaven’s sake, what would Louis Pasteur say about this if he could   witness it all? At first he would be thrilled to see that the work he started in France with rabies and fowl cholera paid off:  vaccination saved millions of lives, improved the quality of life of people all over the world, and at a very low cost.  But then he’d be shocked, frustrated, and angry to realize the lack of a vaccine against arrogance, stubbornness and social irresponsibility. And, malheureusement, that the internet is an equal-opportunity forum that allows stupid ideas to thrive. Especially if they are fueled by human emotions. More on that later.

“Why is it now a problem to get sick? Disease is a natural thing, people should get sick and allowed to recover.  Vaccines are not natural.”  Oh, dear… This statement almost made me lose it. The sheer absurdity of it, the social irresponsibility, the disconnection with the reality of what such diseases cause to human beings.   The words hurt my ears.  But, that’s what she (and other anti-vaccine folks) advocate. Poliomyelitis causes permanent paralysis in 10 to 20% of the people infected. In the house next to mine in São Paulo lived a couple with two kids.  One of them contracted polio as a young child and was permanently confined to a wheelchair.  I remember seeing him on sunny days being brought by his mom to the balcony so he could sit and watch the street.   One of my husband’s best friends, here in the US in Lansing MI, had polio.  He couldn’t run; he walked with steel leg braces and two steel canes, one in each hand.  He was forever sentenced to watching all the play, sports and games of his friends and classmates.   Some images are hard to forget. But nowadays we don’t see these cases anymore.  Still, you don’t have to see them to be horrified by the prospect of a young child paralyzed for life.  And that is what the statement “let them get sick” can do to someone.  Today, in 2015, measles kills 400 people worldwide per day. It’s a death that affects the un-vaccinated rich and poor alike, the well-fed and the malnourished. I can’t comprehend an intelligent person advocating “let them get sick.”  I am the one who’s sick: sick and tired of people equating “natural” with “good.”  Sure, it a potentially good concept, but also potentially naive, and in the case of the anti-vaccine movement, it’s a potentially deadly concept that borders on criminal.

Pertussis_loresBaby suffering from whooping cough – image from Wikimedia 

Now, to the heart of this matter. Why all of a sudden do we witness such a strong pull away from one of THE most beneficial practices in the history of human health, probably matched only by water treatment and antibiotics? It all started with autism and the suspicion that vaccination was responsible for the increase in cases of this horrible illness. To add fuel to the fire, a SINGLE article published in a scientific journal (The Lancet) in 1998 suggested a link between MMR immunization and autism. Many of the most vocal people against vaccination have autistic children, and some state that the onset of the symptoms coincided with their immunization.  One of the “celebrities” who is most aggressive at pushing this agenda is Jenny McCarthy.  I understand she has an autistic boy and and she believes that MMR vaccination caused his illness.  I sympathize with her and his suffering and struggles, as well as those of other parents and children, but that doesn’t make them right. THEY ARE WRONG.  The connection between autism and vaccination was bogus.  It was subsequently extensively studied by many independent groups of scientists in many different countries and laboratories.  Andrew Wakefield, the author of the infamous article connecting vaccination and autism, was rebuked for conflicts of interest,  had his paper retracted and was barred from practicing medicine in the UK.   Can you smell fraud?  The problem is that even in the light of comprehensive scientific evidence to the contrary (summarized here),  disproving ANY connection between vaccination and autism, the anti-vaccine advocates won’t budge. When the articles mounted disconnecting the measles vaccine as a culprit, they changed their focus to its mercury-containing component thimerosal, that was used in the formulation of some of the original MMR vaccines  (current vaccines, BTW do not contain any mercury). When thimerosal was also proven to have nothing to do with autism, they said that the problem was “… too many vaccines are given at the same time.”   The sad reality is this: no amount of scientific evidence is enough to convince those people that their kids did not develop the disease because of vaccination. In fact, in that Frontline episode one father screamed “I don’t give a (expletive) about their data!.” So, instead of accepting that for the time being it is unknown why autism is increasing, and that vaccination has zero impact on it, they follow their gut feelings. From watching the program and reading comments on the internet, I realize that anti-vaccine advocates resist logic and believe instead that scientists are for the most part unethical, and have some hidden financial agenda to hide problems with vaccination.  Nothing could be farther from the truth. Epidemiological studies do not lie:  the numbers are analyzed and correlations made or not made. Anti-vaccine advocates are potentially diverting the focus of scientists from research that may ultimately explain the increases in autism, because they insist like Ms. McCarthy  “we just want them to do the research that is needed.”   In their minds, “research that is needed” are studies that prove a connection they firmly believe in. Otherwise, they will ignore it and fight it. Gut feelings rule.  Fake publications, that are retracted, and the author stripped of his medical license, mean absolutely nothing.   Mr. Wakefield should go to trial because he is indirectly responsible for many preventable illnesses and deaths.

Final words on the importance of vaccination. When you are sick with a bacterial infectious disease, you can take antibiotics to get rid of it. The antibiotic will do good for you, but only you. The beauty of vaccination is that when a person is immunized then others share the benefits,  including individuals that are un-vaccinated. Think about newborns, about those undergoing cancer treatment, or suffering from immuno-suppression of some type. The mechanism behind this side-benefit is called “herd immunity”. When a large enough proportion of individuals in a population becomes immune to an infectious disease (either viral or bacterial), the disease will have difficulty spreading.  In other words, even those non-vaccinated persons get protection by the low probability of encountering the pathogen.  Now, what anti-vaccine advocates seem to think is that their kids don’t need to be vaccinated because other “fools” are doing it, so their kids will be OK by default.  However, herd immunity will not be maintained unless the proportion of immunized people is kept at the target level. This proportion is not hocus-pocus, it’s a carefully calculated number, based on the infectivity of each pathogen. The index used for this calculation is called “Reproductive Number” and reflects the measure of how many people can potentially be infected by a single sick individual. For measles, a highly contagious disease, this number is around 15. Mathematical calculations using the Reproductive Number show that for measles, a level of immunization of around 90 to 95% is required to sustain herd immunity.  Less than that, and the disease will not be kept at bay. You can read more about how the calculations are made by clicking here.

Using predictions of infectivity based on poliovirus, this is what The World Health Organization has to say:  “As long as a single child remains infected, children in all countries are at risk of contracting polio. Failure to eradicate polio from the last remaining strongholds could result in as many as 200,000 new cases every year, within 10 years, all over the world”.

When anti-vaccine advocates preach their illogical stance on this issue, they are acting irresponsibly. Some communities of the USA risk paying a huge price for accommodating such requests and making exceptions due to religious beliefs or gut feelings like  “vaccines cause autism.”  If a serious outbreak of measles, polio, or pertussis takes place, what will those folks say in their own defense? Will they finally admit to being wrong? What good will that do for young parents losing their babies? For kids dying or being affected forever?  If you are ready to go to the streets waving flags and acting hysterically against immunization, you better be ready to stand up and say “I helped create this episode of human suffering and debilitation” when a serious outbreak takes place.  And unfortunately, unless firm action is take by those authorities on the correct side of the issue, I’m afraid it will be just a matter of time before we see the ugly face of an outbreak, in cities like Ashland, OR.

 

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OUR WORK IN THE NEWS!

Our latest publication in the Journal of General Physiology, made the cover of the magazine, and also got us a press-release online… We are thrilled!  

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For the press-release, click here.

“If we can understand exactly how this acquisition process works, we can design, isolate or identify small molecules that inhibit the iron uptake process. Those are potentially antimicrobial agents that could protect people and animals against bacterial disease.”

 (Phillip Klebba, Professor and Head of Biochemistry and Molecular Biophysics, Kansas State University)

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