Posts about medical research

Unexpected Risks Found In Editing Genes To Prevent Inherited Disorders

Mitochondrial replacement seeks to remove genes known to cause genetic defects from embryos in order to allow for a baby to avoid inheriting the defect.

Mitochondrial Replacement Techniques: Ethical, Social, and Policy Considerations from the USA National Academy of Sciences

Accordingly, the committee recommends that any initial MRT clinical investigations focus on minimizing the future child’s exposure to risk while ascertaining the safety and efficacy of the techniques. The recommended restrictions and conditions for initial clinical investigations include

  • limiting clinical investigations to women who are otherwise at risk of transmitting a serious mtDNA disease, where the mutation’s pathogenicity is undisputed, and the clinical presentation of the disease is predicted to be severe, as characterized by early mortality or substantial impairment of basic function; and
  • transferring only male embryos for gestation to avoid introducing heritable genetic modification during initial clinical investigations.

Following successful initial investigations of MRT in males, the committee recommends that FDA could consider extending MRT research to include the transfer of female embryos if clear evidence of safety and efficacy from male cohorts, using identical MRT procedures, were available, regardless of how long it took to collect this evidence; preclinical research in animals had shown evidence of intergenerational safety and efficacy; and FDA’s decisions were consistent with the outcomes of public and scientific deliberations to establish a shared framework concerning the acceptability of and moral limits on heritable genetic modification.

The research in this area is interesting and our ability to help achieve healthy lives continues to grow. The path to a bright future though is not without risk. It requires careful action to pursue breakthrough improvements while minimizing the risks we take to achieve better lives for us all.

Unexpected Risks Found In Editing Genes To Prevent Inherited Disorders

Earlier this month, a study published in Nature by Shoukhrat Mitalipov, head of the Center for Embryonic Cell and Gene Therapy at the Oregon Health and Science University in Portland, suggested that in roughly 15 percent of cases, the mitochondrial replacement could fail and allow fatal defects to return, or even increase a child’s vulnerability to new ailments.

The findings confirmed the suspicions of many researchers, and the conclusions drawn by Mitalipov and his team were unequivocal: The potential for conflicts between transplanted and original mitochondrial genomes is real, and more sophisticated matching of donor and recipient eggs — pairing mothers whose mitochondria share genetic similarities, for example — is needed to avoid potential tragedies.

“This study shows the potential as well as the risks of gene therapy in the germline,” Mitalipov says. This is especially true of mitochondria, because its genomes are so different than the genomes in the nucleus of cells. Slight variations between mitochondrial genomes, he adds, “turn out to matter a great deal.”

Related: Gene Duplication and EvolutionThe Challenge of Protecting Us from Evolving Bacterial ThreatsOne Species’ Genome Discovered Inside Another’s (2007)Looking Inside Living Cells

Eating Nuts May Reduce the Risk of Heart Disease, Cancer and Other Diseases

A large analysis of current research shows that people who eat at least 20g of nuts a day have a lower risk of heart disease, cancer and other diseases. The analysis of all current studies on nut consumption and disease risk has revealed that 20g a day – equivalent to a handful – can cut people’s risk of coronary heart disease by nearly 30%, their risk of cancer by 15%, and their risk of premature death by 22%.

While this is reassuring news to those of us (like me) that frequently eat nuts I am not sold on their evidence. Heath research is prone to overstating the benefits. Still there is little reason to avoid making nuts part of a healthy diet. That is a big part of the reason I have. They offer benefits and maybe even great ones (as indicated in this research) without much risk.

An average of at least 20g of nut consumption was also associated with a reduced risk of dying from respiratory disease by about a half, and diabetes by nearly 40 percent, although the researchers note that there is less data about these diseases in relation to nut consumption.

The study, led by researchers from Imperial College London and the Norwegian University of Science and Technology, is published in the journal BMC Medicine, Nut consumption and risk of cardiovascular disease, total cancer, all-cause and cause-specific mortality: a systematic review and dose-response meta-analysis of prospective studies (open access paper).

The research team analysed 29 published studies from around the world that involved up to 819,000 participants, including more than 12,000 cases of coronary heart disease, 9,000 cases of stroke, 18,000 cases of cardiovascular disease and cancer, and more than 85,000 deaths.

While there was some variation between the populations that were studied, such as between men and women, people living in different regions, or people with different risk factors, the researchers found that nut consumption was associated with a reduction in disease risk across most of them.

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The Challenge of Protecting Us from Evolving Bacterial Threats

I have long been concerned about the practices we continue to use increasing the risks of “superbugs.” I have written about this many times, including: The Overuse of Antibiotics Carries Large Long Term Risks (2005)Are you ready for a world without antibiotics? (2010), Antibiotics Breed Superbugs Faster Than Expected (2010), Entirely New Antibiotic (platensimycin) Developed (2006), Our Poor Antibiotic Practices Have Sped the Evolution of Resistance to Our Last-Resort Antibiotic (2015).

I do also believe the wonderful breakthroughs we make when we invest in science and engineering have made our lives much better and have the potential to continue to do so in many ways, including in dealing with the risks of superbugs. But this is something that requires great effort by many smart people and a great deal of money. It will only happen if we put in the effort.

Winning war against ‘superbugs’

hey won this particular battle, or at least gained some critical intelligence, not by designing a new antibiotic, but by interfering with the metabolism of the bacterial “bugs” — E. coli in this case — and rendering them weaker in the face of existing antibiotics

ROS, or “reactive oxygen species,” include molecules like superoxide and hydrogen peroxide that are natural byproducts of normal metabolic activity. Bacteria usually cope just fine with them, but too many can cause serious damage or even kill the cell. In fact, Collins’ team revealed a few years ago the true antibiotic modus operandi: they kill bacteria in part by ramping up ROS production.

We need to continue to pursue many paths to protecting us from rapidly evolving bacterial risks. Many promising research results will fail to produce usable solutions. We need to try many promising ideas to find useful tools and strategies to protect human health.

Using Rats to Sniff Out TB

Apopo’s African giant pouched rats are being used to sniff out mines and TB

In the face of what the World Health Organisation is calling a global TB epidemic, an innovative tech startup named Apopo is attempting to reverse the harrowing statistics, using rodents to sniff out TB in cough and spit samples.

No ordinary lab rats, Apopo’s African giant pouched rats – affectionately named HeroRats – are extremely sensitive to smell, with more genetic material allocated to olfaction than any other mammal species. They are also highly social animals, and can be trained to communicate with humans.

I have written about these wonderful rats previously, Appropriate Technology: Rats Helping Humans by Sniffing Out Land Mines. As I have stated many time I especially enjoy engineering solutions that use affordable and effective methods to help everyone.

Photo of Hero-rat detecting TB in Mozambique with Apopo staff person

Hero-rat detecting TB in Mozambique

A DNA-screening device that takes up to two hours to analyse each individual sample with 95pc accuracy costs $17,000 and thousands more in upkeep. By contrast, a HeroRat costs $6,500 to train, can probe through hundreds of samples every hour [70-85% accuracy rate], and requires only food, water and cages for shelter.

Keep these innovations coming. The USA needs them also given the massively costly healthcare system in the USA.

The TB sniffing rat program was developed through Apopo in Tanzania.

Related: Rats Show Empathy-driven BehaviorBeehive Fence Protects Farms from ElephantsTuberculosis Risk (2007)Dangerous Drug-Resistant Strains of TB are a Growing Threat (2012)

Healthy Living Greatly Reduces Likelihood of Dying from Cancer

Lifestyle choices can greatly reduce the incidence and death rates from cancer. 4 factors can reduce the incidence of cancer by up to 40% and death rate by 50%: don’t smoke, don’t drink alcohol in excess, maintain a BMI between 18.5 and 27.5, and exercising at a moderate intensity for at least 150 minutes or at a vigorous intensity for at least 75 minutes every week.

Preventable Incidence and Mortality of Carcinoma Associated With Lifestyle Factors Among White Adults in the United States

A substantial cancer burden may be prevented through lifestyle modification. Primary prevention should remain a priority for cancer control.

Cancer is the second leading cause of death in the United States, with 1.6 million new cancer cases and 0.6 million cancer deaths projected to occur in 2016.1 The cancer mortality rate, age-standardized to the 2000 US standard population, decreased from 199 to 163 per 100 000 between 1969 and 2013.2 However, this decline (17.9%) has been modest compared with the dramatic decrease in heart disease mortality (67.5%) during the same period, highlighting the need for further efforts in cancer prevention and treatment.

The study reviewed previous studies and the makeup of the previous studies and available statistics. As they state in the paper: “Because our cohorts’ participants were predominantly whites, to avoid any influence of different racial distributions on the comparison with the general population, we only included whites in the analysis.” They also excluded about 10% of cancers that are believed to have strong environmental factors.

Table Showing a Comparison of Lifestyle Factors in the Low- and High-Risk Groups

In the 2 cohort studies of US white individuals, we found that overall, 20% to 40% of carcinoma cases and about half of carcinoma deaths can be potentially prevented through lifestyle modification. Not surprisingly, these figures increased to 40% to 70% when assessed with regard to the broader US population of whites, which has a much worse lifestyle pattern than our cohorts.

Notably, approximately 80% to 90% of lung cancer deaths could be avoided if Americans adopted the lifestyle of the low-risk group, mainly by quitting smoking. For other cancers, from 10% to 70% of deaths could be prevented. These results provide strong support for the importance of environmental factors in cancer risk and reinforce the enormous potential of primary prevention for cancer control.

Related: A Healthy Lifestyle is More About Health Care than the Sickness Management That We Call Health Care IsBetter Health Through: Exercise, Not Smoking, Low Weight, Healthy Diet and Low Alcohol Intake (2013)Exercise Is Really Really Good for YouPhysical Activity for Adults: Inactivity Leads to 5.3 Million Early Deaths a Year (2012)

International Science Research Scholar Grants

The Howard Hughes Medical Institute (HHMI), Bill & Melinda Gates Foundation, Wellcome Trust, and Calouste Gulbenkian Foundation have announced the International Research Scholars Program which aims to support up to 50 outstanding early career scientists worldwide. The program’s aim is to help develop scientific talent worldwide.

The new international competition is seeking top early career researchers from a wide variety of biomedical research fields. Applicants must have started their first independent research position on or after April 1, 2009. Awardees will be invited to participate in research meetings with scientists supported by the funders. These meetings facilitate the exchange of ideas, stimulate new research, and provide an opportunity for collaborative endeavors within the international scientific community.

  • Awardees will receive a total of $650,000 over five years.
  • Applications are due June 30, 2016.
  • Awardees will be notified in April 2017.

HHMI and its partners have committed a total of $37.4 million for the International Research Scholars Program and will award each scientist who is selected a total of $650,000 over five years. The competition is open to scientists who have trained in the U.S. or United Kingdom for at least one year. Additionally, eligible scientists must have run their own labs for less than seven years, and work in one of the eligible countries.

Nieng Yan

Although Nieng Yan had several grants when she started her lab at Tsinghua University in 2007, she barely had enough money to pay her eight lab members. “In China, there is a limit on the percentage of a grant that you can use to pay people — your graduate students, your postdocs, your technicians, your assistants — to a decent level,” she explains. After struggling to balance her budget for several years, Yan’s scientific achievements and potential landed her an international grant from HHMI in 2012. “The amount of money provided by Hughes is relatively small compared to other programs, but it has the advantage that you can freely decide what to do with it,” says Yan. In fact, HHMI’s science officers encouraged Yan to use her five-year International Early Career Award (IECS) to cover the cost of paying her lab team, explaining that the money could be used in any way that assisted her research. Today, Yan has 15 people working in her lab helping to elucidate the structures of proteins that move molecules in and out of cells. The protein channels and transporters they study are mutated in a number of diseases — including diabetes and cancer — and understanding how they work could help in the development of drugs that block their ill effects. For example, the team recently solved the structure of GLUT1 – a glucose transporter that is often overexpressed in malignant tumor cells. Their data may provide clues for how to inhibit the transporter and perhaps even reveal a way to use it to deliver chemotherapeutic drugs. Photo Credit: Kevin Wolf (AP)

Countries that are not eligible for this competition include the G7 countries (Canada, France, Germany, Italy, Japan, United Kingdom and United States), as well as countries identified by the U.S. Department of Treasury, Office of Foreign Assets Control (OFAC) as being subject to comprehensive country or territory-wide sanctions or where current OFAC regulations prohibit U.S. persons or entities from engaging in the funding arrangements contemplated by this grant program. For this program, such sanctioned countries or territories currently include Iran, North Korea, Sudan, Syria, and the Crimea region of Ukraine.

Related: Directory of Science and Engineering Scholarships and FellowshipsFunding Sources for Independent Postdoctoral Research Projects in BiologyScientific Research Spending Cuts in the USA and Increases Overseas are Tempting Scientists to Leave the USA (2013)HHMI Expands Support of Postdoctoral Scientists (2009)Science, Engineering and Math Fellowships

Gut Bacteria Explored as Medical Treatment – even for Cancer

The interaction between gut bacteria and human health continues to be a fertile area of medical research. It appears to be in the very early days of such research. Of course, as I have said before, headline making news often doesn’t result in medical breakthrough, and even when it does a decade isn’t a long wait for it to happen.

How Gut Bacteria Are Shaking Up Cancer Research

In November, University of Chicago researchers wrote that giving mice Bifidobacterium, which normally resides in the gastrointestinal tract, was as effective as an immunotherapy in controlling the growth of skin cancer. Combining the two practically eliminated tumor growth. In the second study, scientists in France found that some bacterial species activated a response to immunotherapy, which didn’t occur without the microbes.

The complex interactions involved in human health is another area that has huge room for research going forward.

Related: Some Bacteria Might Fight Cancer (2008)Cancer Vaccines (2011)Using Diatom Algae to Deliver Chemotherapy Drugs Directly to Cancer Cells (2015)Webcast of a T-cell Killing a Cancerous Cell (2012)

Using Diatom Algae to Deliver Chemotherapy Drugs Directly to Cancer Cells

I am thankful for scientists doing the time consuming and important research to find new ways to fight disease. Here is an interesting webcast discussing how chemotherapy is used to fight cancer and how scientists are looking to algae to deliver the chemotherapy drugs to better target cancer cells (while not savaging our health cells).

I am also thankful to the funding sources that pay for this research (and for cool explanations of science, like SciShow).

Read more about the genetically engineered algae kills 90% of cancer cells without harming healthy ones. The algae are a diatom and many diatoms look very cool.

Sadly the actual research paper (by government funded university professors) is published by a closed science publisher (when are we finally going to stop this practice that was outdated over a decade ago?). Thankfully those responsible for SciShow are much more interested in promoting science than maintaining outdated business models (in direct contrast to so many science journal publishers).

Related post on cool delivery methods for life saving drugs: Using Bacteria to Carry Nanoparticles Into CellsSelf-Assembling Cubes Could Deliver Medicine (2006)Nanoparticles With Scorpion Venom Slow Cancer SpreadNASA Biocapsules Deliver Medical Interventions Based Upon What They Detect in the Body

200,000 People Die Every Year in Europe from Adverse Drug Effects – How Can We Improve?

A new integrated computational method helps predicting adverse drug reaction more reliably than with traditional computing methods. This improved ability to foresee the possible adverse effects of drugs may entail saving many lives in the future.

Most computer tools employed today to detect possible adverse effects of compounds that are candidates for new medicines are based on detecting labile fragments in the drug’s structure. These fragments can potentially transform to form reactive metabolites, which can have toxic properties. This is what is known as idiosyncratic toxicity and is a big headache for the pharmaceutical industry, as it tends to be detected in late development stages of the drug and even when it is already on the market, often causing the drug to be withdrawn.

Jordi Mestres, coordinator of the IMIM and UPF research group on Systems Pharmacology at the Biomedical Informatics Program (GRIB) states ‘With this study we have contributed to complementing the detection of these quite unstable fragments, with information on the mechanism of action of the drug, based on three aspects: similarity to other medicines, prediction of their pharmacological profile, and interference with specific biological pathways. The optimal integration of these four aspects results in a clear improvement of our ability to anticipate adverse effects with higher confidence, which entails an extremely positive impact on society’.

In Europe, nearly 200,000 people die every year from adverse drug reactions, seven times more than in traffic accidents. An estimated 5% of hospitalisations are due to adverse effects and they are the fifth most common cause of hospital death. In addition, elderly people tend to take more than one drug at the same time, which multiplies the chances of suffering from adverse effects due to potential drug-drug interactions. In an increasingly aging society, this problem is becoming much more serious.

I think interactions is a hugely important area that needs a great deal more research. Doing so is very complex, which means it isn’t surprising so much more work is needed. The work of my father (and George Box and others) on multi-factorial experimentation is a powerful tool to aid this work (and that connection is likely one of the reasons I find the area of interactions so interesting – along with the realization there is so much benefit possible if we focus in that area more). Previous post on this Curious Cat Science and Engineering blog: Introduction to Fractional Factorial Designed Experiments.

The human and financial costs of adverse effects are very high. That is why the discovery of new medicines is increasingly focused more on predicting possible adverse effects at the initial stages of developing a new drug. This work hopes to contribute to setting the path toward a new generation of more reliable computational tools with regard to predicting the adverse effects of therapeutically-relevant small molecules. Advancing large-scale predictive safety at the pre-clinical phase is now becoming closer than ever, with expectations to lead to safer drugs for the entire population.

The research is published in closed science journal so I don’t link to it. I happily link to open science publications. Read the full press release which includes a link to the closed science journal.

Related: Lifestyle Drugs and RiskRoot Cause, Interactions, Robustness and Design of ExperimentsOne factor at a time (OFAT) Versus Factorial DesignsThe Purpose of Mulit-Factorial Designed Experiments11 Year Old Using Design of ExperimentsOver-reliance on Prescription Drugs to Aid Children’s Sleep?

Youyou Tu: The First Chinese Woman to Win a Nobel Prize

The Nobel Prize in Physiology or Medicine 2015 was divided, one half jointly to William C. Campbell (born Ireland, now USA) and Satoshi Ōmura (Japan) “for their discoveries concerning a novel therapy against infections caused by roundworm parasites” and the other half to Youyou Tu (China) “for her discoveries concerning a novel therapy against Malaria”.

Youyou Tu is the first Chinese woman to win a Nobel Prize.

Diseases caused by parasites have plagued humankind for millennia and constitute a major global health problem. In particular, parasitic diseases affect the world’s poorest populations and represent a huge barrier to improving human health and wellbeing. This year’s Nobel Laureates have developed therapies that have revolutionized the treatment of some of the most devastating parasitic diseases.

William C. Campbell and Satoshi Ōmura discovered a new drug, Avermectin, the derivatives of which have radically lowered the incidence of River Blindness and Lymphatic Filariasis, as well as showing efficacy against an expanding number of other parasitic diseases. Youyou Tu discovered Artemisinin, a drug that has significantly reduced the mortality rates for patients suffering from Malaria.

These two discoveries have provided humankind with powerful new means to combat these debilitating diseases that affect hundreds of millions of people annually. The consequences in terms of improved human health and reduced suffering are immeasurable.

image of Artemisinin

via Noble Prize website

Malaria was traditionally treated by chloroquine or quinine, but with declining success. By the late 1960s, efforts to eradicate Malaria had failed and the disease was on the rise. At that time, Youyou Tu in China turned to traditional herbal medicine to tackle the challenge of developing novel Malaria therapies. From a large-scale screen of herbal remedies in Malaria-infected animals, an extract from the plant Artemisia annua emerged as an interesting candidate.

However, the results were inconsistent, so Tu revisited the ancient literature and discovered clues that guided her in her quest to successfully extract the active component from Artemisia annua. Tu was the first to show that this component, later called Artemisinin, was highly effective against the Malaria parasite, both in infected animals and in humans. Artemisinin represents a new class of antimalarial agents that rapidly kill the Malaria parasites at an early stage of their development, which explains its unprecedented potency in the treatment of severe Malaria.

Youyou Tu was born in 1930 in China and is a Chinese citizen. She graduated from the Pharmacy Department at Beijing Medical University in 1955. From 1965-1978 she was Assistant Professor at the China Academy of Traditional Chinese Medicine, from 1979-1984 Associate Professor and from 1985 Professor at the same Institute. From 2000, Tu has been Chief Professor at the China Academy of Traditional Chinese Medicine. She doesn’t have a doctorate, very rare for a Nobel Prize winner in the sciences.

Read the full press release

Related: Nobel Prize in Physiology or Medicine 2012 for Reprogramming Cells to be PluripotentNobel Prize in Physiology or Medicine 2008Parasites in the Gut Help Develop a Healthy Immune System2011 Nobel Prize in Physiology or MedicineVideo showing malaria breaking into cell

Cancer Rates Consistent Across Species Instead of Increasing Due to Body Mass

It would seem sensible to think cancer should be more prevalent in species with a huge number of cells, and thus more cells to become cancerous. But cancer risk doesn’t increase in this way. This interesting, open source paper, sheds some light on what is behind this.

Solutions to Peto’s paradox revealed by mathematical modelling and cross-species cancer gene analysis

Whales have 1000-fold more cells than humans and mice have 1000-fold fewer; however, cancer risk across species does not increase with the number of somatic cells and the lifespan of the organism. This observation is known as Peto’s paradox. How much would evolution have to change the parameters of somatic evolution in order to equalize the cancer risk between species that differ by orders of magnitude in size? Analysis of previously published models of colorectal cancer suggests that a two- to three-fold decrease in the mutation rate or stem cell division rate is enough to reduce a whale’s cancer risk to that of a human. Similarly, the addition of one to two required tumour-suppressor gene mutations would also be sufficient.

We surveyed mammalian genomes and did not find a positive correlation of tumour-suppressor genes with increasing body mass and longevity. However, we found evidence of the amplification of TP53 in elephants, MAL in horses and FBXO31 in microbats, which might explain Peto’s paradox in those species. Exploring parameters that evolution may have fine-tuned in large, long-lived organisms will help guide future experiments to reveal the underlying biology responsible for Peto’s paradox and guide cancer prevention in humans.

Elephants in Kenya

Elephants in Kenya by John Hunter. See more photos from my trip to Kenya.

In another way it would make sense that large animals would have hugely increased risks of cancer. As they evolved, extremely high cancer rates would be a much bigger problem for them. Therefore it wouldn’t be surprising to find they have evolved a way of reducing cancer risks.

Despite these limitations, we found genes that have been dramatically amplified in specific mammalian genomes, the most interesting of which is the discovery of 12 TP53 copies in the genome of the African elephant. We subsequently cloned those genes and identified 19 distinct copies of TP53 in African elephants and 15–20 in Asian elephants [1]. Another potential lead for solving Peto’s paradox is MAL, which is found to have eight copies in the horse genome and two in microbat. This could be an example of convergent evolution where a large animal (horse) and a small, long-lived animal (microbat) both evolved extra copies of the same gene to overcome their increased risk of cancer. Further analysis and experimentation would need to be performed to determine the function of these copies and whether or not they provide enhanced suppression of carcinogenesis.

The researchers have found an interesting potential explanation for how that has been accomplished.

Related: The Only Known Cancerless Animal (the naked mole rat)Webcast of a T-cell Killing a Cancerous CellResearchers Find Switch That Allows Cancer Cells to SpreadCancer Vaccines

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