Science runs in the family

June 18, 2015 § Leave a comment

Claes (left) and Henrik (right) Dohlman at a banquet honoring the elder Dohlman in 2010. Henrik Dohlman credits his father for being a major influence.


Some scientists credit schoolteachers or graduate-school and postdoctoral advisers as their career role models. Henrik Dohlman at the University of North Carolina stays within his family. He credits his father.

“I really look up to him,” he says of Claes Dohlman. “He’s not only done great things professionally, he’s a very kind man.”

“Great things professionally” is a fair description. Claes Dohlman is a well-known figure in vision research. Inducted into the American Society of Cataract and Refractive Surgery’s Hall of Fame in 2004 and the recipient in 2007 of the American Academy of Ophthalmology’s highest honor, the Laureate’s Award, the elder Dohlman who is an emeritus professor at Harvard University, is considered the founder of modern corneal science. His research into corneal physiology established the basis for current clinical practice with dry eye disease, corneal burns, wound healing and corneal transplantation.

Although he retired from university administration in 1989, Claes Dohlman has stayed on as a scientist. At 92, he is the director of Boston Keratoprosthesis Research and Development, which is part of Massachusetts Eye and Ear, where he created and works to perfect a device he is now famous for: an artificial cornea known as the “Boston keratoprosthesis.” The artificial cornea can be used on patients who can’t rely on standard human corneal transplants, such as chemical-burn victims. A prosthetic that resembles a collar button, it is made of medical-grade plastic and titanium. Since cleared by the FDA in 1992, over 10,000 patients have had the device inserted in their eyes.

The older Dohlman turned his full attention to the device in the 1990s, once he retired from being the chair of Harvard’s ophthalmology department, director of his ophthalmology laboratory, and a chief at Massachusetts Eye and Ear.

With a hint of understatement, the younger Dohlman says of his father, “He has a lot of energy.”


From Sweden to the U.S.

Science and medicine surrounded Claes Dohlman as he grew up in Sweden. His father was the chairman of the ear, nose, and throat department at the University of Lund. “It was hinted that there was only one worthwhile profession to consider and that was academic medicine,” remembers Dohlman.  “All my friends were heading for medicine so I followed the path of least resistance.”

Dohlman got an M.D. and finished a residency in ophthalmology at the University of Lund’s Eye Clinic. Drawn by the work of Jonas Friedenwald at Johns Hopkins University on the histochemistry and biochemistry of corneal wound healing, Dohlman did a fellowship with him in the early 1950s in Baltimore, Md. He returned to Sweden to get a Ph.D. in biochemistry from the Karolinska Institute.

A famous retina surgeon in Boston, Charles Schepens, noticed Dohlman’s work. He offered Dohlman a fellowship at Harvard. Having been in the U.S. for the Hopkins fellowship, Dohlman says, he knew that “the possibilities, professionally, were so much greater.”

So in 1958, Dohlman and his wife, Carin, moved to the U.S. with three children. Two years later, Henrik became their fourth child and the first to be born in the U.S. Two more children followed.


The little professor

Henrik Dohlman displayed traits of an academic at a young age. “He was a little professor from the start,” says his father.  “He was always very curious, always eager to lecture people on how things really are and copiously read all kinds of literature.”

He also had a willingness to experiment. Claes Dohlman describes a moment in 1968 when he and Carin opened the front door of their home to a sales representative from a hearing-aid company. All of the adults were confused. The sales representative insisted that a Henrik Dohlman had contacted the company. The parents couldn’t figure out why a hearing-aid sales representative wanted to see an 8-year-old boy.

The confusion cleared when the child admitted to finding an advertisement that offered free testing of a hearing aid.

“I had this image that it would give me super powers, and I would hear what people were saying at great distances,” says Henrik Dohlman, still sounding sheepish almost five decades after the incident. “So I filled out the card, and then the salesman showed up. When he discovered that the person he was about to try to sell a hearing aid to was an 8-year-old boy with perfect hearing, he stomped off.”

Henrik Dohlman with his parents, Claes and Carin, at an UNC graduation event in 2008.

Henrik Dohlman with his parents, Claes and Carin, at an UNC graduation event in 2008.

The younger Dohlman recalls his childhood home in Arlington, Mass., as filled with joyful chaos of a large and close-knit family. “When my father came from work, we all swarmed to greet him and he would be tackled by his kids,” he says. “Dinnertime was masses of spaghetti and conversation.”

But Henrik Dohlman got hints from a young age that his father also was a well-known figure in the community. “Every time I would pass the principal of my elementary school, he’d tousle my hair and say, ‘How’s the son of the famous Dr. Dohlman?’ I figured if my principal knew who he was, then my father must be prominent.”

Education was critical in the Dohlman family. Among the six, two are M.D.s and the rest are Ph.D.s. Henrik Dohlman says his father is very proud of the fact that all his children hold advanced degrees.  “If I can say one thing about my parents, it is that they were exceedingly generous financially,” says Dohlman. “They put six kids through college and then graduate or medical school. It’s something I took for granted when I was growing up. But once I got to college and grad school, I realized what a gift that was, to have no financial barriers to completing my education. That’s my inheritance.”

Henrik Dohlman was the only one to go into the life sciences. His other Ph.D.-toting siblings are economists. He credits his mother for turning him onto biology even though she holds a degree in political science. Carin Dohlman also grew up in Sweden, where, as her son notes, all schoolchildren are taught to appreciate the natural world and revere the 18th-century botanist and zoologist Carl Linnaeus who laid the foundations for modern species nomenclature and ecology. Carin Dohlman shared her love and wonder of nature with Henrik.


Identity of his own

Despite earning a Ph.D. in biochemistry like his dad, Henrik Dohlman, who is also an associate editor for the Journal of Biological Chemistry, is quick to point out that he was always intent on making his way through science as independently as possible. His research portfolio at UNC focuses on understanding the fundamental properties of yeast G protein-coupled receptors, a far cry from clinical corneal research.

Ironically, the first project Henrik Dohlman was involved in as a graduate student landed him in his father’s territory. The younger Dohlman was in the laboratory of Robert Lefkowitz at Duke University in the 1980s. At the time, the laboratory was focused on cloning the β-adrenergic receptor, the first hormone-based G protein-coupled receptor identified and cloned. The work later led to Lefkowitz’s Nobel Prize in chemistry in 2012, shared with Brian Kobilka at Stanford University.

“I thought I was working in an area that had nothing to do with vision research,” says Henrik Dohlman. “But the first thing we noticed about this receptor was it was clearly homologous to rhodopsin, the light receptor.”

Because of the striking similarities between the two systems, Henrik Dohlman’s first scientific conference was the annual meeting of the Association for Research in Vision and Ophthalmology. “It was not only one of my first public presentations, but it was a public presentation in front of about 500 of my father’s friends and colleagues, with my father in the front row,” recounts the younger Dohlman.

Perhaps realizing how unprepared his son was for his first presentation at a national scientific meeting, the older Dohlman pulled him aside and asked to see the slides and hear the talk before the event. “It was a very painful experience for both of us,” recalls his son. “The talk that came out in the end bore no resemblance to what I’d prepared. It was the first and last time I’ve given a scientific presentation with my father in the audience.”

But the younger Dohlman acknowledges that the pain of having his father redo his first public presentation for him was well worth it. “I’m a much better public speaker because of it!” he says with a laugh.


“Just shrug it off”

Besides teaching him the value of a good talk, Claes Dohlman has influenced Henrik in two other critical ways. “Probably the most important one was that I saw from an early age that he really loved his work,” says his son. “That’s not a bad way to go through life.”

Claes Dohlman also modeled what it is to be a good laboratory manager. “He’s always had a positive outlook. He rarely loses his temper. He tries to be generous in assigning credit. He does not get distracted by office politics or idle gossip,” says the younger Dohlman.

When it comes to research, Claes Dohlman knows how to roll with the punches. Something his son says he’s still working on. “There are many failures in this business. There are a lot of setbacks, and there’s no escaping that. You can drive yourself crazy if you let it get under your skin. The best that you can do is brush it off and move onto the next challenge,” says Henrik Dohlman. “I hear my father’s voice in my head saying, ‘Just shrug it off.’”

Mitochondrial replacement therapy: Critical treatment or risky business?

April 10, 2015 § 3 Comments

Mitochondrial Replacement Therapy

Mitochondrial replacement therapy to stop the transmission of mitochondrial disease involves the transfer of nuclear DNA from an affected egg to a donor egg with healthy mitochondria.
Credit: Australian Science Media Centre

What are the risks associated with mitochondrial replacement therapy which is a new technique to prevent mitochondrial diseases? This was a key scientific question asked last week at a meeting held by an Institute of Medicine committee focused on the ethics and social ramifications of MRT.

At the IOM meeting, held on March 31 and April 1 in Washington, D.C., experts presented on numerous ethical, scientific, and legal topics surrounding MRT in order to inform the committee made up of twelve doctors, lawyers, and scientists. The IOM committee was commissioned by the U.S. Food and Drug Administration to explore the ethical and scientific aspects of MRT. The committee will present its findings in a report in early 2016. The spring meeting was the second of five scheduled meetings.

Mitochondrial diseases are caused by mutations or deletions in the 37 genes encoded in the mitochondrial genome. The diseases have a variety of symptoms, including muscle weakness, blindness, dementia, and some cases, childhood death. There are no cures for mitochondrial diseases.

MRT, a process in which the nuclear DNA is transferred from an affected mother’s egg to a donor egg with healthy mitochondria, is intended to stop the transmission of mitochondrial diseases from a mother to her children. The procedure is controversial because it involves destroying fertilized human eggs. Also, critics say it could lead to the slippery slope of nuclear DNA germline modification. This technique has been approved in the U.K. but is still being considered by the FDA.

The scientific presentations at the latest IOM meeting included alternatives to MRT, as well as the possible risks to the children born by MRT, such as epigenetic modifications and haplotype incompatibility. Jacques Cohen, a founder of Reprogenetics, said that pre-implantation genetic diagnosis does not work for all women with mitochondrial diseases and should not be considered a viable alternative.

Carlos Moraes at the University of Miami explained a few alternatives to MRT that reduce the proportion of mutant mitochondrial genomes. In a single mitochondrion, the two to 10 copies of mitochondrial DNA can have different genotypes. Moraes has designed a way to get restriction endonucleases to cut a defective mitochondrial genome, shifting the proportion of healthy mitochondria in cell culture. He recognized that it is not always possible to find a unique recognition sequence in a mutant genome, which is why he also is investigating other targeting systems.

Howard Hughes Medical Institute investigator George Daley at Harvard Medical School talked about potential epigenetic effects of MRT in stem cells. He admitted that epigenetic differences between different stem cell types were considerable, and techniques for analyzing single cells at an epigenetic level are limited. In short, researchers don’t know what the right epigenetic patterns are for a developing embryo, and they don’t have reliable methods to analyze the patterns either.

The fact that different mitochondrial genomes could interact poorly with different nuclear genomes was rather contentious. Doug Wallace at The Children’s Hospital of Philadelphia talked about the evolution of different groups of normal mitochondrial genomes and possible interactions between mitochondrial and nuclear genotypes. Much of his data came from subtle behavioral tests performed on inbred mice strains with swapped mitochondria. He concluded that mitochondrial DNA does influence neural performance and behavior, and that one should ensure that the mitochondrial DNA in the donor and intending mother’s eggs were as similar as possible to reduce these risks.

Cohen rebutted Wallace’s presentation by pointing out the limitations of using subtle behavioral differences in inbred mouse models to conclude anything about the highly heterogeneous human population. Direct debate was not permitted—only the committee members could question each speaker.

It will be interesting to read the committee’s report in early 2016 and see their conclusions about the risks of MRT.

Mollie Rappe

Mollie Rappe, the guest author of this blog post, is a science writing intern at ASBMB Today. You can follow her on Twitter @mollie_rappe .


National Academies report urges higher salaries and better training for postdoctoral researchers

December 10, 2014 § Leave a comment

for-maggie-postThe National Academies released a report today that advocates for improvements in training and salary for postdoctoral fellows in academia. Although postdoctoral training is necessary to pursue careers in academia, it now frequently is associated with poor pay, indefinite terms and uncertain prospects for career advancement.

“The demand for junior research workers has boomed in recent decades, but the number of research faculty positions into which the junior researchers might hope to move has not kept pace,” Gregory Petsko, chairman of the Committee to Review the State of Postdoctoral Experience in Scientists and Engineers that wrote the report, said in a statement. “The result is a system that has created expectations for academic career advancement that in many — perhaps most — cases cannot be met.”

The report urges action in six areas: compensation, term length, position title and role definition, career development, mentoring and data collection.

The report specifically recommends:

1)      Postdoctoral salaries should be increased to at least $50,000 and adjusted annually for inflation. The starting salary at most institutions for many disciplines is $42,000. Furthermore, federal agencies should require institutions to provide documentation in grant proposals about the salaries the postdoctoral researchers will receive.

2)      Postdoctoral appointments should be for a maximum of five years. Funding agencies should assign each postdoctoral fellow an identifier to track them better.

3)      The title “postdoctoral researcher” should be used by institutions only for positions in which the individual receives significant advanced training in research. “Postdoctoral researcher” should not be used for people in positions that are more suitable for permanent staff scientists, such as lab managers, technicians, research assistant professors. The report also urges funding agencies to use “postdoctoral researcher” consistently and “require evidence that advanced research training is part of the postdoctoral experience.”

4)      Postdoctoral training should be viewed by graduate students and principal investigators as only a stage in which to gain advanced research training. It should not be considered the default step after Ph.D. training.

Institutions should make first-year graduate students aware about careers outside of academia. Mentors should become familiar with career-development opportunities at their institutions and through professional societies so that they can better advise mentees. Professional societies should gather information about the range of careers within their disciplines.

Graduate students and postdoctoral fellows should make use of the resources available to them.

5)      Training postdoctoral fellows entails more than just supervision. Mentoring should be emphasized. Postdoctoral fellows should be encouraged to seek guidance from multiple advisers besides their principal investigators, and they should seek out mentoring and resources from professional societies. (Related:  See this recent Nature Careers article about career-development opportunities, including ones at ASBMB.)

The report also calls for better data keeping on postdoctoral fellows. The committee found current data on postdoc demographics, career goals and career outcomes inadequate and out of date. “Only rough estimates of the total number of postdoctoral researchers, and no good information about what becomes of postdoctoral researchers who earned their Ph.D.s outside the United States, exist,” says the report.

The report recommends that that National Science Foundation establish a central database to track postdocs, including nonacademic and foreign-trained fellows. Moreover, funding agencies should “look favorably on grant proposals that include outcome data for an institution’s postdoctoral researchers.”

The last time the National Academies examined postdoctoral training was in 2000. A number of improvements have occurred since then, including the creation of offices of postdoctoral affairs at universities, requirements for mentoring plans in grant proposals to the NSF and some resources for postdocs to explore their career options and make more informed decisions.

However, other aspects have not improved. Data on the number of postdoctoral fellows and how postdoctoral fellows turn out are still inadequate. Moreover, the committee found “no convincing evidence that most postdoctoral researchers are receiving adequate mentoring.” The committee also said that “there is little evidence that universities and mentors are providing adequate information about and preparation for other types of careers.”

The committee appears to want to change the nature of postdoctoral research from a vague transition time back to an active career-development stage. As the committee writes in the preface of the report, “The postdoctoral period should be a defined period of advanced training and mentoring in research and that it should also be, as the majority of the committee members remembered from their own experience, among the most enjoyable times of the postdoctoral researcher’s professional life.”

Three ASBMB members were on the report committee: Petsko of Weill Cornell Medical College; Carol Greider of Johns Hopkins School of Medicine and 2009 Nobel laureate; and Nancy Schwartz of the University of Chicago.

Maggie Kuo is ASBMB Today's science writing intern.

Maggie Kuo, the author of this blog post, is ASBMB Today’s science writing intern.

From country girl to author on most cited paper: Nira Rosebrough Roberts

November 11, 2014 § 5 Comments

Nira Rosebrough Roberts. Photo provided by Lauren Buendia.

Nira Rosebrough Roberts. Photo provided by Lauren Buendia.

“I was a little country girl who really didn’t know much of anything. But I was very good at what I did and we made a good team.” That is Nira Rosebrough Roberts, the technician who worked with Oliver Lowry and two others to develop the Lowry method, a famous way of measuring the amount of protein in a solution.

The Journal of Biological Chemistry paper that describes the method is the most cited paper in publishing history. At the last count on October 7, 2014, the paper had been cited 305,148 times. Roberts’ maiden name, Nira Rosebrough, is second on the paper.

Roberts, now a vivacious 87-year-old widow living a life packed with games of bridge and other fun at an independent seniors’ home in Lexington, Kentucky, landed in Lowry’s laboratory in Washington University School of Medicine in St. Louis by “pure happenstance,” she says.

Roberts grew up in the small town of Bolivar, Missouri, where she excelled in school. “I got very good grades so I was the valedictorian of a very small class,” she says. “There were 44 students.”

Her parents didn’t have money for college so, when she graduated from high school, Roberts first went a junior college called Southwest Baptist University in Bolivar for two years. She was the first one in her family to head to college. But Roberts wanted more so she next decided to enroll at Drury University in Springfield, Missouri.

When she got to the university, Roberts weighed her options. She loved math. But in those days, the only avenue open to a woman with a math degree was teaching. “I didn’t want to be a teacher,” says Roberts.

So, because she enjoyed a chemistry course in high school, she opted to pursue a bachelor’s degree in chemistry with a minor in math. The degree was a four-year program, which Roberts completed in two, graduating magna cum laude in 1948.

Notably, “I’m probably the only B.S. in chemistry who got through school without taking physical chemistry!” she says with a laugh. “My chemistry professor allowed me to take a brand new course called atomic physics instead of physical chemistry, and they gave me a bachelor’s degree.”

Roberts can’t recall how she found out about the technician job at Washington University, but she and three young men headed to the university after they graduated from Drury University. The men entered the medical school, and Roberts began to work for Lowry.

Lowry had been at the institution for a year as the head of the pharmacology department. “We’d meet in the mornings and go over whatever results we had in the afternoons,” recalls Roberts. “I had no idea about biochemistry or anything else when I got there, but I was a good technician.”

She and Lowry had a daily routine. Lowry outlined the experiments needed to be done for the day in the mornings. Roberts made the solutions and did the experiments. Lowry came by to look at the results and discuss them in the afternoons.

Roberts describes Lowry as always brimming with ideas and being an excellent teacher: “I had no idea about biochemistry. But he explained everything to where I could halfway understand it.”

Oliver Lowry. Photo courtesy of the National Library of Medicine.

Oliver Lowry. Photo courtesy of the National Library of Medicine.

Plus, she says, with a delightful chuckle, “He was very handsome!”

The protein measurement method described in the JBC paper relies on a solution called the Folin phenol reagent. The reagent, which consists of phosphomolybdic-phosphotungstic acid, binds proteins treated with copper. The reagent gets reduced, causing a quantitative color change from yellow to blue. The amount of color change is used to calculate protein concentration.

The two other people who pitched in with the protein measurement method were an M.D. named Lewis Farr and another technician, Rose Randall. Farr left research to practice medicine, and Randall was in the Lowry laboratory  for only a few months. Roberts lost touch with them when they left the laboratory. Our staff’s attempts to find Farr and Randall have failed so far. Lowry passed away in 1996.

In 1951, Roberts left the Lowry laboratory. She and her soon-to-be husband, DeWayne Roberts, whom she had met at Washington University, had been eking out life on technician salaries that were less than $2,000 a year. To make more money, they headed to Cactus, Texas, to work at an ammonium nitrate plant. Roberts’ husband worked in the plant and, because women weren’t employed there, Roberts became the administrative assistant to the plant’s personnel director.

In 1953, the couple was back at Washington University with Roberts resuming her technician position in Lowry’s laboratory. She focused on micro-measurement methods while her husband pursued his Ph.D. in pharmacology.

Lowry already had written up and published the protein measurement paper in the JBC by the time Roberts returned to his laboratory. He gave her a reprint of the paper in an olive-green envelope, which Roberts still has somewhere among her possessions. She and her husband left the university in 1957 after he got his Ph.D.

Roberts says she had lost track of the JBC paper in the 1960s and 1970s while she was busy raising three children. She had become a homemaker. Her husband’s work was her only connection to science.

But after Citation Classics mentioned the JBC paper in1977, a coworker of her husband’s noticed it and told them about the paper’s citation record. The paper’s fame clued her family in that Roberts had played an important role in science.

“They were very impressed but they didn’t understand it,” she says “My family didn’t realize what I was doing. They didn’t know what chemistry was or anything. I was just fortunate enough that it was easy for me and I could make good enough grades.”

But even if they don’t understand what exactly Roberts had accomplished with Farr, Randall and Lowry, “they are very proud and so am I.”

Surviving in the Pacific Ocean, bacterial style

September 4, 2014 § Leave a comment

Scientists collected samples during a research cruise in October 2011 along a 2,500-mile stretch in the Pacific Ocean, from Hawaii to Samoa. The transect cut across regions with widely different concentrations of nutrients, from areas rich in iron to the north to areas near the equator that are rich in phosphorus and nitrogen but devoid of iron. [Credit: Brian Dimento, University of Connecticut]

Scientists collected samples during a research cruise in October 2011 along a 2,500-mile stretch in the Pacific Ocean, from Hawaii to Samoa.
[Credit: Brian Dimento, University of Connecticut]

Oceans cover 70 percent of the earth’s surface. Given this vast area, how do you thoroughly study how a particular organism survives in it? In a paper just out in Science, researchers analyzed how a type of cyanobacteria ekes out an existence in a 2,500-mile stretch of the Pacific Ocean. The researchers were able to measure for the first time changes in absolute protein concentrations expressed by the community of this cyanobacterium as it weathered scarcities of different nutrients. In another paper in the same issue of Science, a different group of researchers focused on a particular enzyme that helps marine cyanobacteria and other microorganisms survive under conditions of nutrient deficiency and discovered what makes the enzyme tick.

The oceans harbor “much of Earth’s biological diversity,” points out Mak Saito at the Woods Hole Oceanographic Institution who was the first author on the first Science paper. Researchers want to know how the microorganisms, which are the foundation of the marine food web and are essential to the cycling of biologically important elements, survive in oceans. The researchers want to understand how changes in carbon, phosphorus, nitrogen and other elements, caused by natural means or human activity, affect the survival of these critical microorganisms.

But Saito says experiments to analyze the effects of nutrients on marine microorganisms are difficult to do and tend to only give a glimpse of what’s going on. So Saito’s group turned to proteomic technologies because they could use them to quantitatively study the details of the biochemical changes happening in the microorganisms across the Pacific Ocean. The investigators spent a month on a ship, traveling across the Central Pacific Ocean, from Hawaii to Samoa, and collecting microbial protein samples from as deep as 1 kilometer from the ocean. The path they traveled cut through the northern regions that were rich in iron to areas near the equator that were plentiful in phosphorus and nitrogen but lacked iron. For each sample, the investigators filtered  300-800 liters of seawater over 4-6 hours through 0.2-micron filters and froze the samples.

When they got back to Woods Hole, they used two different proteomic methods to study how the protein content changed in their samples that they took from the 2,500-mile stretch of the Pacific Ocean. Saito says that previous studies identified many proteins in the oceans and their relative abundances. In contrast, the measurements he and his colleagues carried out are the first quantitative marine protein concentration measurements “in units of femtomoles of protein per liter of seawater,” he says. “By measuring the concentrations of proteins, we can map changes in the microbial biochemistry across the ocean basin.”

From their data, Saito and colleagues showed that multiple nutrient scarcities affected the cyanobacterial community they chose to track. Their conclusion refutes the notion on which previous work in the field was based, which is microbial growth and protein production was at the mercy of a single nutrient that was scarcest.

Indeed, “biogeochemists have realised that the availability of more than one inorganic nutrient may simultaneously restrict growth of microorganisms, particularly if the concentrations of the nutrients are linked by biological processes,” says Ben Berks at the University of Oxford in the U.K. who led the team in the second Science paper that identified a critical cofactor for an alkaline phosphatase found in cyanobacteria and other microorganisms. The team on the second Science paper is unaffiliated with Saito’s team on the first Science paper.

The phosphatase, PhoX, was reported to be a calcium-dependent enzyme. “However, we noticed that the purified protein had a purple color and we knew this could not arise from calcium ions,” says Berks. “This observation prompted us to investigate the nature of the PhoX cofactor.”

Although PhoX activity is critical in many microorganisms, the enzyme has not been characterized in detail.  “Possibly it reflects the fact that, although the enzyme is widespread in environmental organisms, it is not present in commonly studied model organisms,” suggests Berks.

The investigators crystallized the enzyme and then used an X-ray spectroscopic technique called micro-PIXE as well as electron paramagnetic resonance spectroscopy to identify the metals that were a part of the enzyme. They identified an iron-calcium cofactor.

Previously PhoX was thought to be a simple calcium-dependent enzyme. Calcium is abundant in seawater. If calcium was readily available, Saito says, “people wondered how microbes were maintaining the PhoA zinc alkaline phosphatase.”

Zinc is a rare commodity in marine environments. Why would a microorganism go through the trouble of relying on zinc when there was plenty of calcium to spare for enzyme activity? Now that Berks and colleagues have shown that PhoX depends on iron and calcium to function, says Saito, it now becomes clear the microorganisms are forced to make do with two different scarce elements.

The discovery of a new enzyme cofactor also means that the work of marine biochemists has a long way to go. As Berks notes, “The work demonstrates that there are still novel biological cofactors to discover within the pool of currently unstudied microbial proteins.”

On being (sort of) scooped by both Carl Zimmer and Ed Yong

April 2, 2014 § 3 Comments

Being scooped once stings. Being scooped twice is a burn. But being scooped by two different prominent science writers makes your soul die.

Unbeknownst to Carl Zimmer and Ed Yong, both of whom have had recent accounts of the parasitic jewel wasp, I too have been working on telling the story of the wasp’s intricate manipulations of the cockroach brain. But I am a victim of a monthly magazine production cycle, the kind in which your story is in the works in February and March and unable to see the light of day until the April issue.

But let’s back up.

Late last year, I came across a poster abstract that had been submitted for our upcoming annual meeting in San Diego. While the abstract briefly mentioned Ampulex compressa, commonly known as the jewel wasp, and cockroaches, I fixated on the authors saying that they had milked wasps to do proteomic analyses of their venom. How do you milk a wasp?

Because I was dying to know how wasps get milked, I decided to write a press release about the work described in the abstract. But when I interviewed Ryan Arvidson and Michael Adams at the University of California, Riverside, about their work, I grew increasingly excited. This was an amazing story. Screw the press release. I wanted to write the story myself for ASBMB Today.

Once I hung up the phone, I burst into the office of my editor, Angela Hopp, babbling about zombie roaches and wasps being shoved inside pipette tips for milking. My excitement, if not coherent, must have been infectious because she agreed the story was too good for us to give away to other reporters.

Then I interviewed Fred Libersat, who had introduced Ampulex compressa to Adams. Libersat sent me a 1942 paper by entomologist Francis Xavier Williams. After I finished reading Williams’ paper, I sat there for a few minutes, dumbfounded.

I never had read a scientific article as poetic and vivid as Williams’. As I do with anything that strikes me as funny, ridiculous or fascinating, I sent it to Angela, urging her to read it if she had time. She always makes time.

She wrote back:

“My dear, this is a remarkable specimen. And I think it’s a great opportunity to do something really amazing.”

sketchThe next day, there were sketches from Angela laid on my office chair of how I could weave together the narratives of the proteomic analysis of the wasp venom and Williams’ descriptions. (Bless the woman, she is sharp with words but can’t draw wasps to save her life.)

The main frame of story came together shortly thereafter (and it later went through iterations too many to count).

And then Zimmer landed the first punch. On Saturday, March 1, Angela emailed me two lines:

“I’m so sorry.

Fighting that sinking feeling of being second-best, I thought:

Well, this Zimmer story came out on Feb. 27. For once, I hope people don’t recall prose weeks later and will read my story in April with fresh eyes and enthusiasm. Anyway, Zimmer’s story focuses a lot on the anatomy of the wasp. My story is more about the molecular composition of the venom.

Convinced that the wasp-roach relationship was rich enough to be mined for many stories, I wrote back:

“Trying to find some solace in the fact that Carl Zimmer and I think alike…”

I was still excited about my story.

Neither Angela nor I complained about the rounds of revisions we inflicted on ourselves because we both wanted the story to be special. We also made sure we had stunning photographs. As our unflappable designer, Marnay Harris , developed the layout (turns out, she hates looking at cockroaches), I grew more optimistic. My story had a different feel from Zimmer’s previous coverage. Certainly, using sections from Williams’ paper as part of my narrative gave my story a stand-out character.

Then, last week, my editor wordlessly sent me this link:

In the second blow, Yong in March had spoken about the jewel wasp in a TED talk. That is, I’m guessing he did, because neither my editor nor I can bring ourselves to watch it*.

I replied with only one word, but I had to use four symbols and an exclamation point instead of letters because I was using my work email account.

I do think it’s fitting that this story wound up in an issue with a print date of April 1, April Fools’ Day. How foolish I was to think that I could, at least for a short window, own the story of the jewel wasp.

*Angela requests that I report that, after being guilted by the first draft of this blog post, she did watch Yong’s TED talk.

The Indian-American I didn’t know: Yellapragada Subbarao

March 24, 2014 § 7 Comments

Discovering Yellapragada Subbarao at the "Beyond Bollywood" exhibit. Photo by Rajendrani Mukhopadhyay

Discovering Yellapragada Subbarao at the “Beyond Bollywood” exhibit. Photo by Rajendrani Mukhopadhyay

I had never heard of Yellapragada Subbarao until I entered the exhibit “Beyond Bollywood: Indian Americans shape the nation.” My ignorance shocked me. As someone who holds bachelor’s and Ph.D. degrees in biochemistry and writes about biochemistry for a living, I thought I knew the movers and shakers in the field, both present and past. But here I was, ignorant about Subbarao and how he was involved in the discovery of ATP and phosphocreatinine and developing the chemotherapy drug methotrexate.

The exhibit, hosted by the Smithsonian Institution at the Natural History Museum (second floor, behind the gem and mineral store), showcases how Indians have come to the U.S. since the 1800s to carve out their livelihoods. As a newly minted U.S. citizen who was born in India and has roots in Kolkata, this exhibit held great personal appeal.

With mementos, video clips, photos and more, the exhibit describes how Indians, among other things, shaped U.S. immigration and naturalization policies and integrated into their new homeland. Parts of the exhibit were familiar, so familiar that it felt like stepping into a home of a childhood friend. I knew about Jhumpa Lahiri, Mindy Kaling and Nina Davuluri. Some parts enlightened me. I didn’t know about Brandon Chillar, but that wasn’t surprising because American football continues to puzzle me despite my 16 years here. But Subbarao stopped me short.

I didn’t recognize his photo or name. Yet, as I was about to walk by toward the section about music, I caught sight of “ATP” and “methotrexate” in the text next to his photo. I stopped in my tracks. I knew those words intimately so why didn’t I know “Subbarao”?

Concepts about ATP are taught in introductory molecular biology courses. Methotrexate pops up often in the scientific literature and continues to be used today in chemotherapy. If I knew about James Watson, Francis Crick, Gunter Blobel, Bruce Alberts and so on, why was the name of a fellow Indian biochemist unknown to me?

It turns out my ignorance wasn’t entirely my fault. According to my subsequent readings, Subbarao never was in the limelight (I am uncertain if he deliberately shunned it or if forces beyond his control didn’t give him greater prominence in the annals of biochemistry). Even two years after Subbarao’s death, a journalist named Doron Antrim wrote in 1950, “You’ve probably never heard of Dr. Yellapragada SubbaRow. Yet, because he lived, you may be alive and well today.”

(The spelling of Subbarao is confusing. I’ve seen two versions: Subbarao, according to the exhibit, and SubbaRow, according to his first U.S. publication in the Journal of Biological Chemistry. In my opinion, the latter sounds like an attempt to anglicize his name so non-Indian speakers didn’t butcher it as much. But since he himself used “SubbaRow” in his scientific publications, I will use it for the rest of the post.)

SubbaRow’s biography mirrors that of many Indian immigrants. After training as a medical and Ayurvedic practitioner, SubbaRow left Madras, India, in 1923 (Madras is now called “Chennai“). He carried with him an admissions letter to the Harvard University School of Tropical Medicine as he traveled on steamers. He left behind a pregnant wife. Their son was born in 1924 but died before his first birthday from erysipelas, a bacterial infection. SubbaRow never saw the boy, his wife or his family in India once he set sail for the U.S. His journey and studies in the U.S. were funded by his father-in-law.

In the U.S., Sabbarao did his Ph.D. work with Cyrus Hartwell Fiske. With Fiske, Sabbarao developed a simple color test for determining the phosphorus content, both inorganic and organic, in biological tissue (the paper describing the test is now a JBC Classic). Thanks to this test, Fiske and SubbaRow were able to demonstrate that phosphate in muscle existed in the form of phosphocreatine, an organic compound that is used as an energy source during muscle contraction. Later, in a Science paper in 1929, Fiske and SubbaRow described the isolation and characterization of ATP.

In 1940, SubbaRow left his position as a teaching fellow at Harvard to become the associate director of research at Lederle Laboratories (an arm of American Cyanamid, which was bought by Wyeth, which in turn was acquired by Pfizer). At Lederle, working with Sydney Farber, a former colleague from Harvard, SubbaRow’s team designed methotrexate, an antifolate drug. (To read more about Farber, check out “The Emperor of All Maladies” by Siddartha Mukherjee, another Indian-American highlighted at the “Beyond Bollywood” exhibit.)

SubbaRow’s other accomplishments included finding a drug for filariasis and discovering aureomycin, the first antibiotic that worked against both Gram-positive and Gram-negative bacteria. His achievements were so many that American Cyanamid later named a fungus in SubbaRow’s honor: Subbaromyces splendens. The Government of India released a commemorative stamp with him on it in 1995, his birthday centennial (were I living in India in 1995, I probably would have heard him then). In India, the National Institute of Indian Medical Heritage pays tribute to him.

A Washington Post reporter gave a lukewarm, almost derisive, review of the “Beyond Bollywood” exhibit, saying it felt like “a vanity project.” But vanity is all about wallowing in oneself, disregarding anyone or anything else.  I feel “Beyond Bollywood” went beyond vanity. The exhibit showed that there was still room for me to learn about topics of which I thought I was an expert.

At the “Beyond Bollywood” exhibit. Photo by Gautam Saxena.

Why I voted for the Rosalind Franklin bobblehead

November 22, 2013 § Leave a comment

I credit the actress Juliet Stevenson for helping me chose a career in science. When I was 18, as part of the “A” level course in biology, my high school biology teacher let us watch a made-for-TV movie called “Life Story” (its other name, “Race for the Double-Helix,” immediately gives away what the movie was all about). Stevenson played the role of Rosalind Franklin (Jeff Goldblum played James Watson, before his Jurassic Park fame).

Until I became acquainted with Franklin’s character in that film, Marie Curie had been the only female scientist about whom I knew anything. But Curie was almost a mythical, ghostly figure, and I had no idea what daily life had been like for her.

Stevenson’s portrayal of Franklin was my first glimpse of how a female scientist navigated life. In Parisian cafes, with cups of coffee on the table and surrounded by friends, Stevenson’s Franklin was warm and generous, with a hearty laugh. But around Maurice Wilkins, Francis Crick and Watson, Franklin turned into a cold, impenetrable, aggressive woman who took great pride in and care with her meticulous work and closely guarded her data.

As a teenager growing up in the conservative Middle East surrounded largely by people from patriarchal societies, I felt a kinship to Franklin that I couldn’t articulate but recognized. I am fun-loving and gregarious. But in our small science classes at school, there was fierce gender rivalry. I and a few female friends were outnumbered by boys. Boys were expected to become doctors, engineers and scientists. Girls had to prove they were good enough to be doctors, engineers and scientists. I had to be sharp and ready with the correct answers, always demonstrating that I could beat the boys on what was supposedly their turf. My notes, which I diligently rewrote every day after school in colored pens in neater penmanship than possible in class, were highly coveted but I refused to share them with anyone. If I didn’t get the highest score on tests and exams, I at least made sure I beat the boys. (I was willing to share the two top rungs of scholarship with my best friend.)

I couldn’t put my finger on it then, but watching Stevenson’s portrayal of Franklin told me that I had been doing what needed to be done to succeed in science. As time took me through a bachelor’s degree and then a Ph.D. in the life sciences, I learned to meld the two sides of me, mixing in fun with learning and not being afraid to do things that were considered feminine, such as baking cakes for my grad school labmates (for two years, I was the only woman in the lab) and leaving stern notes by the balance to clean it up signed “Lab Mom.” I also realized that women like Franklin had left footsteps for me to follow and that I had it easier because of women like her.

So as I pondered my choices for a female scientist bobblehead earlier this week, I felt I had to give a nod (literally!) to the woman who first showed me how to be a scientist.

Today’s Supreme Court hearing on gene patents as seen on Twitter

April 15, 2013 § Leave a comment

I compiled a list of notable tweets about today’s Supreme Court hearing on the Association for Molecular Pathology vs Myriad Genetics case. You can find them here.

Funny #SoGodMadeAScientist Tweets

February 4, 2013 § 3 Comments

  1. “I need someone who will endure failure, failure, failure in the lab and still not quit.” #SoGodMadeAScientist
  2. It may have taken me 7 days to create the universe but it’ll be a while before you guys figure this stuff out. #SoGodMadeAScientist
  3. God got annoyed watching people admiring the universe without even seeing the coolest parts of it. #SoGodMadeAScientist
  4. “Billions of years ago I made protons…and magnetism. Gonna be wicked cool when someone figures out NMR!” #SoGodMadeAScientist
  5. God realized that the only thing to do with some people was put them on reality TV. But there were no televisions #SoGodMadeAScientist
  6. “I need someone to come into lab at 5 am, start a Western blot, run stats on yesterday’s data, & code behavior videos” #SoGodMadeAScientist
  7. I needed someone to work out that the pork prohibition was about trichinosis…and fix it so farmers could make bacon #SoGodMadeAScientist
  8. God knew DNA looked pretty cool at the EM level, but needed someone to invent an electron microscope #SoGodMadeAScientist
  9. Needed: someone to devote their life to one protein, in one cell type, with no real KO phenotype, and no western blot #SoGodMadeAScientist
  10. I need someone who can look at a harsh world and not recoil in fear but ask how to make things better for all of us. #SoGodMadeAScientist

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