James Ntambi, second from right, with members of his laboratory

What is the best way to encourage science in Africa?

Some African scientists come to the United States to train and then return to their home countries to teach and perform research (read about two examples here).

James Ntambi took a different approach - after receiving his Ph.D. he remained in the United States and now leads a lab at the University of Wisconsin, where he trains African scientists and teaches Americans what life is like in Uganda.

Born and raised in Mukono, Uganda, Ntambi studied biochemistry at Makerere University in Kampala. In 1980 he received a Fulbright award to attend graduate school at the Johns Hopkins University School of Medicine in Baltimore - with every intention of returning to Africa. For his Ph.D. thesis he studied the biology of trypanosomes, parasites that cause sleeping sickness (endemic in parts of sub-Saharan Africa).

After receiving his Ph.D. Ntambi decided he needed more research experience. He remained at Hopkins for a research fellowship in the lab of Dan Lane, studying how fat cells develop. Though seemingly unrelated, the way in which fat cells and trypanosomes mature and develop is similar, and Ntambi hoped to learn more about trypanosomes by studying fat - intending to return to Africa to study trypanosomes. 

At the end of his fellowship in 1989, however, Ntambi got a job as an assistant professor at Georgetown Medical School. He decided that he could improve science in Africa by remaining in the U.S. but returning to Makerere to teach.

With funding from the NIH, Ntambi and a colleague from the City College of New York took 10-15 students from minority institutions (historically black colleges) to Makerere University every summer between 1990 and 1995. Ntambi paired the American students with their Ugandan counterparts and taught them all basic molecular biology techniques. The NIH funding also allowed Ntambi to set up a small laboratory at Makerere.

Now a full professor at the University of Wisconsin in Madison, Ntambi runs a similar program as part of a course called ‘international health and nutrition.’ Every fall, students in the course study public health issues that affect Africa - as part of their standard classroom work - and then spend three weeks in Uganda. Not just in Kampala, but also in rural Uganda, which comes as quite a shock to students from Wisconsin.

Ntambi stresses the value of teaching Americans about the difficulties people face in Africa. “After those three weeks, when they come back here, they are different people,” Ntambi told me. “They come back with a totally different perspective.”

Ntambi also hosts scientists from Uganda in his laboratory for three or four months at a time. These mini-sabbaticals allow Ugandan scientists to learn new techniques and develop networks with scientists in the U.S. In reality, most of the techniques they learn are conceptual - genetically engineering mice is standard practice at research institutions in the United States, but is not available in Uganda.

A visit to Ntambi’s laboratory is likely to encourage African scientists because of the exciting, cutting-edge work. Ntambi and his group recently showed that a protein in the skin regulates how the entire body stores fat. Mice genetically engineered to lack the SCD1 protein in the skin are lean, and do not become obese even when fed a diet high in fat. Surprisingly, the same is not true of mice genetically engineered to lack this protein in other parts of the body.  If you remove SCD1 from the liver or from fat tissue, the mice still became obese on a high-fat diet. It is the protein’s presence in the skin that regulates fat storage throughout the body.

We know the brain, the liver and the gut communicate with one another to monitor and control energy intake, storage and expenditure. Ntambi’s work suggests that the skin is part of this metabolic control apparatus as well. But while scientists have identified some of the hormones that the liver, brain and gut use to communicate with one another, it’s not known how the skin tells the body to store fat. Does the skin communicate with the liver or the brain or the gut, or directly with fat cells?

Ntambi is working to answer these questions. Meanwhile, he continues to lead students to Uganda, teaching African students that diet and exercise can prevent obesity and diabetes, stressing prevention over treatment. In Uganda, Ntambi explained, treatment is too expensive. Prevention is the only option.

Image by PLoS One

A mobile phone with microscope attachment.

Bulky, expensive microscopes help diagnose tuberculosis, sickle cell disease and malaria. In the developing world diagnosis is hampered by lack of equipment and difficulty accessing remote and rural areas.

If you can’t bring the people to the microscope, then bring the microscope to the people.

Daniel Fletcher and his colleagues at the University of California in Berkeley developed an attachment to a mobile phone, allowing it to be used as a portable microscope powerful enough to see blood cells and diagnose disease. Images are captured using the phone’s built in camera. Analysis and diagnosis can be made on the spot, or the image can be e-mailed from the phone to a clinic for more detailed examination.

The resolution of the device is about 1.2 micrometers (µm), good enough to see many different types of cells. Red blood cells are 7-8 µm in diameter; a human hair is between 60 and 120 µm wide.

What makes this even more impressive is that the team did not modify the mobile phone itself, a Nokia N73. They used the phone’s built-in camera (3 megapixels) and the phone’s photo capture software and settings. They could not control shutter speed or aperture and had limited control over exposure conditions.

Image by PLoS One

A human blood sample viewed with a mobile phone microscope. Arrows point to sickle-shaped red blood cells, a sign of sickle cell disease. The white scale bar (bottom right) is 10 µm long.

Despite these limitations, the mobile phone microscope appears to be able to detect misshapen red blood cells (a sign of sickle cell disease) and malaria-infected blood.

Fletcher’s team was also able to detect tuberculosis bacteria in sputum using fluorescence microscopy, a technique that normally requires an expensive and delicate light source and filters. Instead the scientists used a rugged LED as a light source and incorporated the filters into their device. After staining a blood sample with a fluorescent dye that specifically sticks to tuberculosis bacteria, you shine blue light on the specimen, and the bacteria will glow green. This green glow is very dim, requiring filters to insure that only green light reaches the camera.

Image by PLoS One

(a) Fluorescence image of Auramine O-stained TB sputum sample. (b) Enlarged view of two tuberculosis bacilli from red-outlined area in (a). Scale bars are 10 µm long in (a), 1 µm long in (b).

In the future, installing standard imaging software on the phone will allow users to count the number of tuberculosis bacteria in a sample automatically.

Fletcher and his colleagues seem to be following a standard model for commercializing their invention, which is to sell it in the developed world and use the profits to provide the device free, or at low cost, in the developing world. (Check out the award-winning nonprofit company Diagnostics For All to learn about an unconventional approach to commercialization.)

Ideas include using the device to count blood cells in patients undergoing chemotherapy for cancer treatment, which often make patients more susceptible to infections. Using the mobile microscope to perform routine cell counts at home would reduce the number of hospital visits, reducing exposure to pathogens.

Here’s another use: a microscope for children. Toy science sets abound, but microscopes are difficult to use in the field. To encourage a young biologist, provide your child with this microscope attachment to his or her mobile phone. In addition to texting friends, your child can now examine plants and bugs up close in the field. This could be a great way to instill a love of science and the natural world.

Source: Breslauer, D., Maamari, R., Switz, N., Lam, W., & Fletcher, D. (2009). Mobile Phone Based Clinical Microscopy for Global Health Applications PLoS ONE, 4 (7) DOI: 10.1371/journal.pone.0006320

Image by Satre Stuelke

A CT scan of a McDonald's Big Mac sandwich.

Check out Stuelke’s Web site for more radiology art.

As you might know some weeks ago the H1N1 swine influenza became part of our lives, at least here in Mexico. I’m 22 years old and I’d never lived through anything like that before.

At the beginning we felt that we were in a movie; it was kind of scary and everything was all over the place. But the good thing was that the government gave us day-by-day new useful information and preventive tips. These made us to be calm and knowing that if we followed all the instructions and if we kept the unity we could fight against the virus. And you know what… we are doing it!! Which is great!

Well, as I told you, swine influenza became part of our lives; I was on exams when everything started. On Sunday I went back to the city where I study, then on Monday I did the exam and at 12 o’clock they told us that the president gave the order that all schools of Mexico from all levels would be closed until May 6th… so we had to postpone everything.

I’m about to finish college so we have many things approaching. For example: it was supposed that we would be done on June 22nd (that day was my last final exam), we didn’t know what would happened with the final date. At that point, we really hoped that we could go back on May 6th, wishing everything would get better!!! Not just for school, but for everybody, peace, security, to feel good going out and being with people… because at this moment those things just didn’t exist… It was weird.

Through time things finally got better, the virus is still in Mexico, but it is more controlled because they know more about it which is pretty good in order to fight against it. But also, because all people is following the instructions and we are taking care of ourselves and of the others.

During two weeks there no schools, no places to go out, no restaurants, not many things to do…

But I can tell you that I never wished so deeply like this time, in HAVING school, I DIDN’T want to be at home doing nothing, I never thought that I would want that haha!! Because as I said it was so close to the final date that we had many things to do.

It’s also kind of weird, because we have to follow many “instructions or orders” in order to be healthy. For example we have to wash our hands before we enter and after every class, we have to use anti-bacterial lotion all the time, we can’t borrow or lend anything. There are many nurses in the whole school, we have to answer some questions everyday, we can’t say hi with hugs, hands and kisses, which is weird because we are used to that.

We have to remember that everyday, sometimes you just do things as usual, but then you think and you realize that you can’t, or other people tells you. But it is amazing how little kids (from kindergarten) can tell you EVERYTHING that we have to do or not, and they actually remember them always, I was surprised about it.

That’s pretty much everything; in my case, my school life was affected, but many people have to deal with many, many things.

We can see it as we had to reform our social and individual behavior in sanitary and healthy habits. We had to leave behind some usual things and adopt many new things that we have to learn and make them as usual. Sometimes it’s weird, maybe hard, but I’m glad about the kindness to everybody, how people is unified and how we respect each other… in order to keep healthy.

With this, you can see that together, we can fight and do everything for the common good.

A 62 year old man was detained while trying to enter the United States because immigration officials could not detect his fingerprints, which had deteriorated as a side effect of cancer treatment.

The man, Mr. S, was being treated for throat cancer with the drug capecitabine. Side effects include hand-foot syndrome, which can cause redness, swelling and cracked, flaking or peeling skin on the soles of the feet and palms of the hand.

Mr. S’s throat cancer was in remission, but he had been taking capecitabine for three years to prevent the cancer from returning.  He developed a mild case of hand-foot syndrome, not severe enough to “affect his daily activities and function.”

When travelling from Asia to visit family in the United States, immigration officials detained Mr. S for more than four hours because they could not detect his fingerprints.

According to the report, international airports in the United States “have been fingerprinting foreign visitors for many years. Each visa applicant has two index fingerprint images taken from and they are matched with millions of visa holders to detect whether the new visa applicant has a visa under a different name. These fingerprints are also matched to a list of suspected criminals.”

Mr. S - who was not aware of his missing fingerprints before travelling to the United States - was ultimately released and advised to travel with a letter from his oncologist explaining his condition in the future.

Source: “Travel warning with capecitabine” by M. Wong, S.-P. Choo and E.-H. Tan, published in the Annals of Oncology online on May 26, 2009 (doi:10.1093/annonc/mdp278).

Yes. “Human influenza viruses can survive and maintain their infectiousness for several days when they are deposited on banknotes,” according to a 2008 study by Yves Thomas and his colleagues at the Central Laboratory for Virology in Geneva, Switzerland.

Scientists spotted different types of flu virus onto Swiss francs and found that they survived from a few hours (naked virus) to more than a week (virus mixed with respiratory mucus).

The results depended on the type and concentration of flu virus.

According to the study, Swiss banknotes are mostly cotton covered by a nonporous resin. Bills from other countries may be composed of different materials, and this could affect viral transmission. “Whether similar results would be obtained with banknotes from other countries and with different characteristics needs to be studied,” the authors wrote.

In an interview with Reuters, Thomas said, “Our studies have convinced us that it is possible to catch flu from banknotes, but the chances are very, very slim and there is no cause for concern among the general population.”

SmartMoney had this to say in a recent story:

To be sure, many kinds of frequently touched surfaces could temporarily harbor the flu virus. Broadly speaking, scientists consider the risk of transmission in this way to be low, particularly if hand-washing and other hygiene measures are practiced, says Dr. Philip Tierno, director of clinical microbiology and immunology at New York University’s Langone Medical Center and author of “The Secret Life of Germs.”

Three things must happen for a flu virus to be transmitted from one person to another via money. First, a person who is infected with the swine flu must sneeze or cough onto the bill or blow their nose and leave remnants of their mucus on the currency. Next, an uninfected person would need to touch the money while the virus is still present.

Finally, that person would need to put their contaminated hand in their mouth or pick their nose, says Dr. Murray Grossan, an otolaryngologist at Cedars-Sinai Medical Center in Los Angeles.

The best defense against infection: follow public health guidelines and wash your hands frequently.

Source: “Survival of Influenza Virus on Banknotes” by Yves Thomas, Guido Vogel, Werner Wunderli, Patricia Suter, Mark Witschi, Daniel Koch, Caroline Tapparel and Laurent Kaiser, published in Applied and Environmental Microbiology, May 2008.

Scientists are human, believe it or not, and sometimes we get so lost in the details that we fail to appreciate the fundamentals.

In diseases where myelin, the fatty insulation surrounding nerves, is destroyed, the working assumption is that restoring myelin will reverse symptoms of the disease — yet this basic premise never has been proven.

In demyelinating diseases such as multiple sclerosis, the body repairs some of its damaged myelin, and there is partial recovery of neurologic function, but it’s unclear how much of the recovery is due to the repaired myelin. Demyelination is accompanied by inflammation, so reducing inflammation could be the primary path to recovery. There is evidence that nerves might adapt to better conduct electrical impulses when myelin is damaged. The brain also might compensate for damaged circuitry by relying more on undamaged pathways.

This assumption is critical: if restoring myelin restores function, then scientists should focus their efforts on restoring myelin; if restoring myelin fails to restore function, then scientists should pursue a different strategy to treat demyelinating diseases.

Ian Duncan and colleagues at the University of Wisconsin recently showed that remyelination restores function in cats suffering from a unique demyelinating disease. Pregnant cats, fed a diet of irradiated food for months, developed severe neurological symptoms such as paralysis and vision loss. (Nobody knows why this happens to pregnant cats; a similar diet does not cause problems in rodents.)

These cats had widespread demyelination of the brain and spinal cord (but not peripheral nerves). Putting the cats back on a normal diet restored myelin, and the nerves remained intact. The myelin did not repair itself completely – in most areas the restored myelin was thinner than normal, but this seemed to be sufficient, because the cats recovered neurological function.

These results are tantalizing, because “it absolutely confirms the notion that remyelinating strategies are clinically important,” Duncan said in a statement.

As for the cats, many questions remain. How does the irradiated diet specifically target myelin, sparing the nerves (is the radiation destroying an essential vitamin, leading to deficiency)? What is unique about pregnant cats, making them susceptible? How does the immune system respond?

Source: “Extensive remyelination of the CNS leads to functional recovery” by I. D. Duncan, A. Brower, Y. Kondo, J. F. Curlee, Jr. and R. D. Schultz, published in PNAS online on April 2 (doi: 10.1073/pnas.0812500106).

Meet Ute Scholl, a 25 year old physician who defined a new clinical syndrome, and then identified the genetic mutations that cause the disease – all in less than one year.

Ute grew up in Aachen, Germany, interested in science and medicine. Hoping to combine the two, she attended medical school in Aachen and after a brief research fellowship in Hannover, came to the United States in March 2008 to work in Richard Lifton’s lab at Yale.

She plans to return to Germany in 2010 for a medical residency and ultimately hopes to work as a physician and a scientist, treating patients in the clinic and studying their disorders in the lab.

“Communication is a very important part of clinical medicine,” Ute told me, explaining why it’s important that she receive her clinical training in Germany, among German-speaking hospital staff and patients, rather than in the United States.

Ute is interested in identifying DNA mutations that cause kidney disease. There are hundreds of genetic diseases that affect the kidneys. For many we don’t know the cause and, consequently, have no cure.

After arriving at the Lifton laboratory, she was given a stack of hundreds of medical records of patients with kidney problems. Many patients displayed symptoms affecting other parts of the body also. Ute screened these records and found five people with similar symptoms: All suffered from seizures, deafness, ataxia (problems walking and controlling their limbs), mental retardation, and electrolyte imbalance (potassium and magnesium deficiencies and elevated blood pH, signs of kidney disease).

Nobody had ever described a disease with these symptoms. None of these patients have Bartter or Gitelman syndrome, diseases with similar electrolyte problems.

If this were the 19th century, Ute might have named the disease after herself and stopped there. But 21st century DNA sequencing and hybridization technology offers a chance to identify the underlying DNA mutation.

From the family history information, Ute and her colleagues thought the disease would be autosomal recessive, meaning the disease strikes males and females equally (so the mutation is not on the X or Y chromosome), and patients with the disease must possess two copies of the mutated gene, one inherited from each parent (homozygous). The parents, who don’t suffer from the disease, each have one normal copy of the gene and one mutated copy (heterozygous).

To identify the mutation, Ute and her colleagues looked for long stretches of DNA that were identical in both copies of a patient’s genome (homozygous). Every human genome contains differences in single bases of DNA scattered throughout. These differences, called single nucleotide polymorphisms, are often used to identify people in criminal investigations.

In this case, Ute was looking for a long stretch of homozygous single nucleotide polymorphisms in the same region of every patient’s genome, which would suggest that the identical piece of DNA was inherited from each parent. Odds are that the mutated gene would be found here.

The genome analysis, led by Murim Choi, identified a region of DNA with 2.5 million base pairs on chromosome 1, a region containing more than 70 genes. How to find the correct one? Ute took a candidate approach, guessing that if there was a single gene responsible for all the problems, it should be turned on in the relevant tissues, in this case the brain, ear and kidney.

Ion channels, a family of proteins that allow ions, such as potassium, to flow into and out of cells, fit the bill. (Some ion channels are specific for potassium, some for sodium, some for multiple ions, and so forth.) The brain, ear and kidney all require ion channels for proper function.

Among more than 70 genes in the region, there were two ion channels. Ute sequenced the KCNJ10, which codes for a well-understood channel that lets potassium ions into cells. gene

Lucky Ute. Every patient had two mutated copies of KCNJ10, and every mutation is predicted to interfere with its normal function. Unaffected parents had only one mutated copy, as you would expect.

Even luckier Ute. In 2000 other scientists genetically engineered mice lacking KCNJ10, and these mice had symptoms similar to the human patients. This saved Ute years of work and strongly supports the conclusion that mutations in KCNJ10 cause the human disease.

The frequency of this disease is unknown. Thus far there are only five known patients, but Ute hopes that her work will help physicians identify others. She is now studying how mutations in the KCNJ10 potassium channel cause this disease.

In the old school medical tradition, Scholl-Lifton syndrome would have been an acceptable name, harking back to the practice of naming diseases after those who describe them (such as Alzheimer’s, Parkinson’s and Creutzfeldt–Jakob diseases). Instead, Lifton has proposed the acronym SeSAME: Seizures, Sensorineural deafness, Ataxia, Mental retardation, Electrolyte imbalance.

Source: “Seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (SeSAME syndrome) caused by mutations in KCNJ10” by Ute I. Scholl, Murim Choi, Tiewen Liu, Vincent T. Ramaekers, Martin G. Häusler, Joanne Grimmer, Sheldon W. Tobe, Anita Farhi, Carol Nelson-Williams and Richard P. Lifton, published in PNAS online March 16 (doi: 10.1073/pnas.0901749106).

In February I wrote about using CT scans to analyze fossils. Now I have uncovered another unusual application of the technology: Art.

Satre Stuelke, a third-year medical student at Weill Cornell Medical College in New York, is putting everyday objects into a scanner and producing works of art.

He told me that during his first year in medical school, he thought about using a CT scanner to “analyze culturally significant objects, looking for some sort of pathology,” much like we scan humans looking for something out of the ordinary.

His Web site now includes dozens of images, including an iPod, a McDonald’s BigMac sandwich, and a Barbie doll (check her out on the left).

A CT scan reveals that Barbie has a “rather detailed skeletal structure, most extensively present in the legs.” Much of Stuelke’s descriptions use the passive voice and anatomical terms of medical imaging. An iPod: “Behind the screen and to the most cephalic extreme of the body, a gray battery pack can be seen …. Note the headphone jack in the upper right part of the image proximal to the battery pack.”

Stuelke attended medical school at the University of Iowa from 1988 to 1990, but dropped out to become an artist. After attending graduate school at the Art Institute of Chicago, he established himself in the art world with a faculty position in New York and more than 60 art shows.

A confluence of events – the September 11, 2001, attacks (which occurred 1,600 meters from his work), a search for obstetricians in preparation for having a baby, and the increasing lack of challenge in the art world – led Stuelke to return to medical school.

Stuelke is now in the unusual position of being a third-year medical student in his fifth year of medical school. He received no credit for the time he spent in Iowa, which might be just as well. He says that he remembers some of his previous medical training, but a lot has changed in 20 years, particularly genetics, immunology, developmental biology and endocrinology.

The university allows him to use an older CT scanner that is only used for research, and only when scientists are not using it. Stuelke remembers asking whether he could put a frozen dinner in the scanner, for artistic purposes. The medical director eventually answered, “we could support the arts.” You can see that result below.

The New York Times covered Stuelke’s work on March 23, and today his pager was beeping with media requests. His attending physician, Dr. Erica Jones, generously gave him the day off, which explains why he had time to speak with me.

After he receives his medical degree, Stuelke plans to specialize in – what else? – radiology.

The scientific community is buzzing now that President Obama has lifted the ban on federal funding for human embryonic stem cell research. In his announcement, the president was careful not to overstate the therapeutic promise of stem cells, but other sources, including some news outlets, have been less cautious. I’m going to follow up on that point by discussing a recent study published in PLoS Medicine that shows just how little we know about using human embryonic stem cells to treat disease.

Ataxia telangiectasia is a devastating and rare genetic disease with no cure, marked by difficulty walking and controlling one’s limbs, impaired eye movements, slurred speech and immune deficiencies. Patients usually die by their early twenties. Many symptoms are due to cells dying in the cerebellum, the part of the brain that coordinates movement. One idea is that stem cells from the brains of human embryos could replace the dying cells in the cerebellum of patients with ataxia telangiectasia.

In May 2001, a 9-year-old boy with ataxia telangiectasia was taken to Russia for the first of three injections of stem cells from fetal brain cells. In February 2005, the boy, suffering from recurring headaches, was examined by neurologists at Sheba Medical Center in Israel. MRI scans showed lesions at the base of the brain (near the cerebellum) and in the spinal cord. The latter tumor was surgically removed. Analysis of the DNA from tumor cells and the patient’s blood cells indicated that the tumor cells did not originate in the patient. The tumor cells must have grown from the transplanted stem cells. (Many tumor cells possessed two X chromosomes, indicating that they are female, but the patient is male.)

This study might teach us something about brain tumors. One theory is that stem cells acquire mutations that lead to unchecked growth; this small population of cells multiplies and forms a tumor. The results of this study suggest it is possible that brain tumors could come from stem cells. Of course, these were stem cells from fetuses implanted into a diseased brain – treating the fetal stem cells with growth hormones before injection could have triggered them to form tumors. Another possibility is that stem cells from fetal brains are more predisposed to unrestricted growth than other types of stem cells, or that the brain of a 9-year-old with ataxia telangiectasia is an environment more conducive to tumor growth than a normal juvenile or adult brain.

Clearly more research is needed to understand how stem cells grow.

Injecting this boy with stem cells does not appear to have been conducted as part of a clinical trial with multiple participants and rigorous follow up. Detailed methods describing how the fetal cells were grown and analyzed in dishes before injection were not published. From the methods that were provided to the Israeli researchers who analyzed the tumor, “cells of various size and form” were used, suggesting that many different types of fetal brain cells were injected into the boy.

I’ll leave the authors with the final word:

“Conventional therapies such as chemotherapy, radiotherapy, and bone marrow transplantation used to treat life threatening diseases are associated with morbidity and mortality. Our findings therefore do not imply that the research in stem cell therapeutics should be abandoned. They do, however, suggest that extensive research into the biology of stem cells and in-depth preclinical studies, especially of safety, should be pursued in order to maximize the potential benefits of regenerative medicine while minimizing the risks.”

Is the promise of stem cell therapy exaggerated? How much preclinical study is required before a therapy should be tested in humans?

Source: “Donor-Derived Brain Tumor Following Neural Stem Cell Transplantation in an Ataxia Telangiectasia Patient” by Ninette Amariglio, Abraham Hirshberg, Bernd W. Scheithauer, Yoram Cohen, Ron Loewenthal, Luba Trakhtenbrot, Nurit Paz, Maya Koren-Michowitz, Dalia Waldman, Leonor Leider-Trejo, Amos Toren, Shlomi Constantini, Gideon Rechavi, published in the February 2009 issue of PLoS Medicine (doi:10.1371/journal.pmed.1000029)