With the theme of Shimon Peres’s recent Presidential Conference being “Facing Tomorrow,” it was only natural that the future of science and medicine was a major topic, and thousands of people listened in rapt attention to a variety of lectures.
Brain science received special focus during the convention as a number of universities, hospitals and technology manufacturers held an exhibition on brain science in a large hall not far from the deliberations. The exhibits represented universities throughout Israel – the Hebrew University of Jerusalem, Ben-Gurion University of the Negev in Beersheba; the University of Haifa, Tel Aviv University and Bar-Ilan University in Ramat Gan. Among the hospitals represented was Haifa’s Rambam Medical Center.
Young people, including scientists at these institutions, manned the exhibits during the two full days of the conference and spoke to passersby about the discoveries and trends.
The brain research panel was moderated by Hebrew University Prof. Eilon Vaadia, director of the Edmond and Lily Safra Center for Brain Sciences and The Jack H. Skirball Chair and Research Fund in Brain Research (ELSC) at HU. Vaadia called for the evolution of medicine from disease treatment to disease prevention.
“This thing we all have on our heads was involved in what was thought to be intriguing and a mission impossible,” he said. “But now our challenge is realistic. We believe we will be able to understand completely how the brain works,” said Vaadia, who the day before helped inaugurated the new building for ELSC on the university’s campus. “We intend to discuss this wondrous voyage into ourselves.”
He pointed out that there are more synapses in the brain than stars in our galaxy. “It looks impossible, but it is true.”
The best, he said, “is yet to come. But even today, we can look at electrical activity of the brain and modify it. We can condition patterns to become different. We will able to understand what a person wants to do. New technologies will be used to make new discoveries that will help mankind. We will be able to create human-like machines or robots.”
PROF. YADIN Dudai, a leading neurobiologist at the Weizmann Institute of Science in Rehovot, spoke next. His research focuses on the investigation of memory systems in the brain, whether memory tells the truth and the interaction of individual memory with the social milieu.
“How will we relate to the other – humanoid robots that are like us? This certainly creates anxiety in people if the robots are very similar to us. Nurse robots have been used in hospitals abroad, but if patients are not demented they feel uncomfortable when they encounter humanoid robots as nurses.”
One would think that memory is about the past – events that happened in real life, suggested Dudai. “But this is not true. Memory is not necessarily about the past or what happened in reality. Memory is not monolithic, there are many types – and most of them we have without being able to use them. If you drove here, you didn’t pay much attention to the road unless you saw a police car in the mirror. There is memory when [we] pay attention and other memory that we don’t notice.”
Episodic memory, said Dudai, “is what happened to us. You can change them a few hours after you experience them. When you remember what happened, you can probably change it by redepositing it in long-term memory. We change our memories quite a lot.” Memory, Dudai continued, “is not faithful to reality. Remember, you do mental time travel to the past. You can also do mental time travel to the future and can imagine what will happen.”
Prof. Richard Frackowiak, director of the department of clinical neuroscience at the CHUV University Hospital in Lausanne.
Switzerland, confessed to the audience: “I am a frustrated neurologist. We don’t know the causes of dementia. We know brains can compensate for degeneration that causes dementia. Today, we use magnetic resonance instruments [MRIs] and other devices to see the normal brain; before, we could see only when a neurosurgeon opened up the head.”
Alzheimer’s disease, the main form of dementia, will take on epidemic proportions in the decades to come. Frackowiak, deputy director of the international Blue Brain Project to create a functional model of the brain, said, “We want to open brain databases, computerize anonymous information from all hospitals in the world to find abnormal results. The problem of dementias has to has to be solved.”
Prof. Henry Markram, a neuroscientist at the Swiss Federal Institute for Technology, founded and directs the eight-year-old Blue Brain Project and is coordinator of the Human Brain Project, one of two 10-year, billion-euro “Flagship Projects” approved by the European Commission.
“This year, the European Commission took a giant step for mankind to simulate the human brain. We have massive responsibility, because it means building the equivalent of a new Hubble Space Telescope that will look inside the brain and discover what exactly is going wrong in brain disease. We need to build a virtual biological copy,” said Markram.
PROF. IDAN Segev, the director of HU’s department of neurobiology and an expert in computational neuroscience, heads a team that uses computational and theoretical tools to study how neurons compute and dynamically adapt to their environment.
In recent years his group has worked as part of the Human Brain Project to help model a whole piece of the mammalian cortex.
Their ultimate goal is to unravel how local fine variations within the cortical network underlie specific behavioral function and possibly create either brain diseases or healthy and individual brains.
“Our same genes make the heart and the brain,” said Segev. “Sir Alan Lloyd Hodgkin and Sir Andrew Fielding Huxley won the Nobel Prize for their work in discovering The Spike. They wrote an electrical equation that looks like a spike in brain activity. One can regulate all brain activity by writing equations and simulate biological phenomenon that can be described mathematically. If you can’t write an equation to depict this, you can’t really understand it. So we will be able to simulate a piece of the brain to become Parkinson’s or epilepsy or depression. I could then probe the model and fix the biological problem to get rid of the disease,” Segev concluded.
Dr. Inna Slutsky, a senior lecturer at Tel Aviv University’s Physiology and Pharmacology Department and the Sagol School of Neuroscience, concluded the panel discussion.
Her research is focused on understanding the basic mechanisms that maintain synaptic plasticity and memory function and initiate memory dysfunction in Alzheimer’s disease.
“In the past decade there hasn’t been even one drug to improve Alzheimer’s. We need to know mechanisms that initiate a gradual transition from physiology to pathology – from a healthy to a sick brain. We need to create neuronal networks with defined properties that could reverse brain dysfunction.
We must then identify the molecules that are involved. We have to merge brain physiology and molecular pathology to get the answer. I hope that in the coming decade, we will be able to bring about a real solution.”
THE SECOND major scientific forum at the conference was dedicated to the future of medicine. The session was moderated by Rambam Medical Center director-general Prof. Rafael Beyar, a senior interventional cardiologist, expert in biomedical engineering and former dean of the Technion’s Rappaport Faculty of Medicine.
“Israel is part of the the effort of bringing medicine forward,” he said. “We lead the world in patents per capita and have 700 companies involved in hi-tech medicine fields, including cardiac mapping, swallowed cameras, surgical roots, focused ultrasound, and bioinformatics” Beyar said.
Prof. Henri Atlan, a former biophysics professor in Paris and director of the Human Biology Research Center and the Department of Medical Biophysics and Nuclear Medicine at the Hebrew University-Hadassah Medical Center, explained that in personalized medicine, treatment is adjusted to the individual’s genetic makeup.
“The DNA sequence of every person is unique, except for identical twins. But it isn’t true that genes determine everything. We know that two identical twins are not the same – not only psychologically but also their nervous, immune and other systems. If identical twins have a mutation that produces a high probability of disease, it isn’t certain that both will get it. And one sibling may get it earlier and the other later or in a more aggressive manner.”
“Gene activity,” explained Atlan, “is controlled by other genes, as well as molecules and proteins. It isn’t dependent on DNA alone.”
People mistakenly believe that the future is in their genome and that by buying a kit to test themselves they will know in advance every disease they can expect, Atlan said.
“Truly personalized medicine won’t be achieved quickly – or at all. Research results have to be reproducible in other patients but if medicine is personalized to only a small number of patients because they have different diseases, it will be hard to prove,” he concluded.
Prof. Dina Ben-Yehuda is head of the hematology department at Hadassah University Medical Center in Jerusalem’s Ein Kerem. A leading researcher in the molecular biology of blood cancers, epidemiology and gene therapy, she recently designed a protein connected to cell death that is now being developed to fight cancer.
A type of leukemia named chronic myeloid leukemia (CML) is a model for personalized medicine, she said. For this disease, an oncogene named BCR/ABL and the cancer are linked.
“The future is already here. Bone marrow transplants were performed on patients before 2000. But fewer than 20 percent of patients were suitable because they were effective only in young people. Many died. But then the Novartis company developed a drug named Gleevec (imatinib) that binds to the gene site and prevents the entrance of proteins. The gene remains inactive so there is no cell death and no CML.”
Most patients today are in complete remission, but some developed resistance to Gleevec as CML cells created a mutation.
However, somewhat different drugs have been produced that can overcome the mutation. More than half a century after researchers identified this kind of cancer, “we can say that CML is curable, but it isn’t clear yet whether patients have to take the drug for life.”
“We have to learn to demystify disease,” suggested Dr. Leroy Hood, president and founder of the Institute for Systems Biology and one of the world’s leading scientists in molecular biotechnology and genomics. A key participant in the Human Genome Project, he advocated a “systems approach to medicine.”
“If you want to understand how a radio works, you naturally take it apart. But that isn’t enough. You have to study the electronic circuits. That’s what systems biology is about – components and interactions and dynamics of behavior. Disease is caused by digital information of the genome and environment. Some people respond to drugs, and some don’t. So if you know who is sensitive before taking drugs, you can reduce complications and the costs of medication. This could lead to the democratization of healthcare. Data will be dirt cheap. All parts of the healthcare industry will have to rethink their business plan, and some will become dinosaurs that can’t cope.”
PROF. HOWARD Cedar – a recipient of many prestigious international and Israel awards, who conducts pioneering cancer research at the Hebrew University Faculty of Medicine, put his finger on the importance of prevention.
“When I started medical school in New York 50 years ago, the dean said:‘You all think you came to learn how to cure diseases. But it isn’t true. The doctor’s role is to prevent disease.’ Today, this is so obvious.
But it is still very hard to do. Preventive medicine – not only to fix a problem but actually make sure it doesn’t happen – needs a different level of research. The emphasis today is on wellness.”
Cedar also discussed his 35 years of work on discovering a process to make proteins.
“Each one has a little place in a ‘book’ on how to make it. The ‘book’ can be annotated.
One goes over the ‘text’ and puts emphasis on certain things and make changes. Annotation tells you how to read it. The body puts markings on the ‘book’ to note what should be read in this cell or another. From this, we learned a lot. In cancer, this annotation system is disrupted, so cancer cells behave badly. It isn’t specific for any cancer,” said Cedar, “but is a general process. This approach is a new way to look at disease and may even lead to a way of slowing down or preventing diseases.”