A new study led by the paleogenetic laboratory of the Steinhardt Museum of Natural History at Tel Aviv University and the University of Haifa analyzed DNA from ancient local winegrape seeds discovered at archaeological excavations in the Negev. One seed was found to be almost identical to the Syriki variety used today to make high-quality red wine in Greece and Lebanon, while another seed is a relative of the white variety called Be'er, still growing in deserted vineyards in the dunes of Palmachim.

Exported to Europe

The genetic study was led by Dr. Pnina Cohen and Dr. Meirav Meiri of the paleogenetic lab at the Steinhardt Museum of Natural History at Tel Aviv University. The seeds were found at archaeological excavations led by Prof. Guy Bar-Oz from the School of Archaeology and Maritime Cultures at the University of Haifa, in collaboration with researchers from the Israel Antiquities Authority. Other participants included researchers from the University of Haifa, the Weizmann Institute, Bar-Ilan University, and research institutions in France, Denmark, and the UK. The paper was published in the leading scientific journal PNAS.

"The findings include large winepresses, jugs in which the exclusive wine, exported to Europe, was stored, and grape seeds preserved for more than a thousand years. This industry gradually declined following the Muslim conquest in the 7th century, since Islam forbids the consumption of wine." - Prof. Guy Bar-Oz

"Archaeological excavations conducted in the Negev [in Israel] in recent years have revealed a flourishing wine industry from the Byzantine and early Arab periods (around the fourth to ninth centuries A.D.), especially at the sites of Shivta, Haluza, Avdat, and Nizana, which were large, thriving cities at the time," says Prof. Guy Bar-Oz from the University of Haifa.

"The findings include large winepresses, jugs in which the exclusive wine, exported to Europe, was stored, and grape seeds preserved for more than a thousand years. This industry gradually declined following the Muslim conquest in the 7th century, since Islam forbids the consumption of wine."

"The cultivation of winegrapes in the Negev was renewed only in modern times, in the state of Israel, mostly since the 1980s. This industry, however, relies mainly on winegrape varieties imported from Europe."

Avdat Excavation (photo: Tali. Erickson-Gini and Scott Bucking)

Extracting DNA

One especially interesting finding was a large hoard of grape seeds, discovered on the floor of a sealed room at Avdat. The researchers explain that these seeds have been relatively well preserved thanks to protection from climatic phenomena such as extreme temperatures, flooding, or dehydration. To learn more about the seeds, in the hope of discovering which varieties they might belong to, the researchers prepared to extract their DNA in the paleogenetic lab.

"The science of paleogenomic uses a range of advanced technologies to analyze ancient genomes, primarily from archaeological findings," explains Dr. Meiri from the Steinhardt Museum of Natural History at Tel Aviv University. "Since the DNA molecule is very sensitive and disintegrates over time, especially under high temperatures, we usually get only small pieces of DNA, often in a poor state of preservation. To protect them we work under special conditions: the paleogenetic lab is an isolated clean laboratory, with positive air pressure that keeps contaminants out, and we enter it in sterilized 'spacesuits' familiar to everyone from the COVID pandemic." 

To begin with, the researchers looked for any organic matter remaining in the seeds. For this purpose, they used FTIR (Fourier-transform infrared spectroscopy) – a chemical technique applying infrared radiation to produce a light spectrum that identifies the sample's content. Finding remnants of organic matter in 16 seeds, the researchers went on to extract DNA from these samples.

Ancient local winegrape seeds from Shivta, Israel (photo: Prof. Guy Bar-Oz, The University of Haifa)

Ancient Grapes - Still Around Today

The extracted DNA was sequenced, with an emphasis on about 10,000 genomic sites where variety-specific features are usually found, and the results were compared to databases of modern grapevines from around the world: In 11 samples, the quality of genetic material was too poor to allow any definite conclusions. Three of the remaining samples were identified as generally belonging to local varieties. Finally, the two samples of the highest quality, both from around 900 A.D., were identified as belonging to specific local varieties that still exist today.

The discovery was quite extraordinary:

• One seed was found to belong to Syriki, a known Middle Eastern variety with a long history of cultivation in the Southern Levant and Crete, still used today to make high-quality red wine in Greece (where it is known to have arrived from the east) and in Lebanon. Since winegrapes are usually named after their place of origin, it is quite possible that the name Syriki is derived from Nahal Sorek, an important stream in the Judean Hills. Moreover, this variety may even appear in the Bible – in Jacob's blessing to his son Judah: "He will tether his donkey to a vine, his colt to the choicest branch (soreka); he will wash his garments in wine, his robes in the blood of grapes (Genesis 49, 11); and perhaps also suggested in the giant cluster of grapes brought back by the men sent by Moses to explore the land:  "When they reached the Valley of Eshkol (identified by some as Nahal Sorek), they cut off a branch bearing a single cluster of grapes. Two of them carried it on a pole between them" (Numbers 13, 23).

• The other high-quality seed was identified as related to Be'er, a white winegrape variety still growing in the sands of Palmachim on Israel's seashore, in remnants of vineyards probably abandoned in the mid- 20th century. For the first time ever, the researchers were able to use the genome of a grape seed to determine the color of the fruit, discovering that it was in fact a white grape - the oldest botanical specimen of a white variety ever identified. Be'er, a unique local variety, endemic to the land of Israel, is used today by the Barkan winery to make a special white wine of its own.

"The wonderful thing about paleogenetics is that sometimes, tiny items can tell a big story. This is exactly what happened in this study. With just a bit of DNA extracted from two grape seeds we were able to trace continuity in the local wine industry - from the Byzantine period, more than a thousand years ago, to the present day." - Dr. Meirav Meiri

Tiny Items Tell a Big Story

"The wonderful thing about paleogenetics is that sometimes, tiny items can tell a big story," says Dr. Meiri. "This is exactly what happened in this study. With just a bit of DNA extracted from two grape seeds we were able to trace continuity in the local wine industry - from the Byzantine period, more than a thousand years ago, to the present day."

"We believe that our findings are also significant for Israel's modern wine industry, which has been growing and thriving in recent decades. Today, most varieties grown here have been imported from Europe, so that the local conditions are not optimal for them. Local varieties can be more suitable for the local climate and soil, especially in the desert region of the Negev. Our study opens new paths for restoring and improving ancient local varieties, to create winegrapes that are more suitable for challenging climatic conditions such as high temperatures and little rainfall."

Tiny items can tell a big story. Ancient winegrape seeds under a Microscope from Avdat (photo: Prof. Guy Bar-Oz, The University of Haifa)

The study was led by Mor Taub, a research assistant in the laboratory of Prof. Yossi Yovel, head of Tel Aviv University’s Sagol School of Neuroscience and faculty member of the School of Zoology at The George S. Wise Faculty of Life Sciences. The study’s findings were published in the journal BMC Biology.

Mor Taub explains: “At the peak of pregnancy, bats carry about 20 percent more than their normal body weight, and it is clear that this excess weight impacts their flying capacity. In this study, we wanted to check whether and to what extent pregnancy affects bats’ echolocation ability, their sonar."

"Bats’ sonar is based on the emitting and receiving of strong and frequent sounds in order to map their surroundings. To make these sounds, bats, like us humans, need to transfer high-pressure air from the lungs through the vocal cords, or vocal membranes, which involves many muscles, such as the chest and diaphragm. We wanted to see if the excess weight from pregnancy affects the production of sounds.”

Prof. Yossi Yovel

To this end, Prof. Yovel and his colleagues taught bats to search for and land on a small landing pad in a flight room in the bat laboratory at Tel Aviv University’s Garden for Zoological Research. They recorded the echolocation of two groups: pregnant bats and non-pregnant bats. The researchers found that the rate at which the pregnant bats emitted sounds was significantly lower than that of the control group, with 20% greater intervals between each sound.

Prof. Yovel, Kadar Family Award for Outstanding Research recipient, explains that “bats change the rate of the sounds they make in accordance with the level of difficulty of the task. The average rate is about ten calls per second, but when the bat lands, this rate can increase to 100 calls per second. The pregnant bats produced sounds at a rate of only about seven per second and flew a little slower and lower."

"Obviously, this slowing down is likely to affect their hunting. When a bat makes fewer calls, it gathers less information about the environment, its chance of colliding with objects increases, and its chance of finding food decreases — and this is at a time when the bat needs extra food to sustain the fetus in its womb. In the second phase of the study, we used a computer simulation to simulate the effect of the decreased rate of calls on the bats’ performance, and indeed, we saw that the slowed rate makes it more difficult for the bats to locate prey.”

“This is the only evidence we found in the professional literature showing that pregnancy affects mammals’ sensory abilities.” - Mor Taub

Preserving the Vulnerable

The bats in the experiment were of the Kuhl's pipistrelle species, tiny bats that weigh only about six grams (when they are not pregnant). These bats are very common in Israel, and feed mainly on mosquitoes. Despite their weight, bats can live for decades, and their pregnancies are therefore also relatively long, lasting about four months.

Previous studies conducted on other species of bats have shown that during pregnancy, bats tend to change their diets. To date, the assumption was that this change in diet was due to the bats’ difficulty in flying, but the current study raises the possibility that the change may also be due to their sensory difficulty in detecting certain types of prey.

“This is the only evidence we found in the professional literature showing that pregnancy affects mammals’ sensory abilities,” says Mor Taub. “We assume that there are similar cases in other species as well, but this is the first time that researchers have been able to measure and demonstrate the impairment empirically. Beyond the scientific interest, it is important to preserve mammal species in the wild, especially during pregnancy and newborn care, since animals are particularly vulnerable during this period.”

The study was led by Prof. Yair Bar-Haim, Director of the Adler Center for Child Development and Psychopathology, and of the Center for Traumatic Stress and Resilience at Tel Aviv University, together with research students Gal Arad and Omer Azriel from The School of Psychological Sciences at the Gershon H. Gordon Faculty of Social Sciences at Tel Aviv University Other collaborators included the NIH, the Tel Aviv Sourasky (Ichilov) and Sheba Medical Centers, and Prof. Amit Lazarov of TAU. The paper was published in the prestigious American Journal of Psychiatry.

"About 4-12% of the population will develop social anxiety disorder at some stage of their lives. Quite often, people with this disorder avoid social situations – at a heavy interpersonal, professional, and economic price." Prof. Yair Bar-Haim

Prof. Bar-Haim explains that "about 4-12% of the population will develop social anxiety disorder at some stage of their lives. Quite often, people with this disorder avoid social situations – at a heavy interpersonal, professional, and economic price. At present, psychiatry and psychology offer sufferers two types of treatment: SSRI (Selective Serotonin Reuptake Inhibitor) drugs, such as Cipralex, and CBT (Cognitive-Behavioral Therapy). CBT requires 12-20 sessions with a qualified clinical psychologist, in which symptoms are relieved through gradual exposure to the cause of anxiety. Thus, while effective, CBT is a complex treatment necessitating the presence of a highly skilled therapist and requiring patients to face their deepest fears, a requirement that often leads to treatment dropout.

"Because CBT is demanding, expensive, and not readily accessible, many patients turn to medication. However, psychiatric drugs like Cipralex have their own drawbacks: first, some patients prefer not to use psychiatric drugs; second, entire populations, such as young children, pregnant women, and individuals with specific diseases, cannot take SSRI drugs; and third, in some cases the drug has certain side effects."

The research team (left to right): Prof. Yair Bar-Haim Gal Arad and Omer Azriel

Simple and Patient-friendly

Now, researchers from TAU have developed a third option, which is easy-to-use, quick and simple, and apparently no less effective than psychiatric drugs. Moreover, since the treatment is highly patient-friendly, a much lower dropout rate may be expected.

In the clinical trial, 105 Israeli adults with social anxiety disorder were assigned into three groups: one group was treated with SSRI drugs, in this case Cipralex; a second group was treated with GC-MART; and a control group. After ten 30-minute training sessions, about 50% of the patients provided with the new therapy demonstrated significant improvement in their symptoms - a result similar to the outcome reported for patients who took Cipralex.

"With efficacy similar to that of an existing first line drug treatment, the new treatment does not require the patient to take medications regularly. The new treatment is simple and patient friendly." Prof. Yair Bar-Haim

"The therapy we developed is based on eye-tracking combined with a musical reward," explains Prof. Bar-Haim. "The patients choose the music they would like to hear – Israeli, classical, hip hop, etc., and is shown a simulation of a crowd on a computer screen. Usually, individuals with social anxiety disorder tend to dwell on scowling or threatening facial expressions, quickly picking them out and unable to look away. Consequently, they often interpret the crowd or social situations as hostile, negative, or critical. People without social anxiety disorder, on the other hand, prefer to focus on positive or neutral faces in a crowd. In the new therapy, the music chosen by the patient provides positive feedback for a normal focus of attention on facial expressions in the crowd presented on the screen. Gradually, through training, patients’ biased attention is normalized, and symptoms recede. All participants in our trial underwent a comprehensive clinical assessment both before and after the treatment and were also asked to report on the symptoms and their severity. Results indicated that the new treatment significantly reduced symptoms of social anxiety, with an efficacy that is similar to that of SSRI drugs."

"Our findings are encouraging for both therapists and patients. With efficacy similar to that of an existing first line drug treatment, the new treatment does not require the patient to take medications regularly. The new treatment is simple and patient friendly. It does not necessitate the prolonged intervention of a highly skilled psychologist, but rather interaction with social images on a screen, and therefore potentially offers accessible, effective, and convenient treatment for social anxiety disorder," concludes Prof. Bar-Haim.